Cardioprotective effects of KATP channel activation during hypoxia in goldfish Carassius auratus
Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA
* Author for correspondence (e-mail: jcameron{at}wellesley.edu)
Accepted 19 May 2005
![]() |
Summary |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: hypoxia, ATP-sensitive K+ channels, KATP, nitric oxide, cardioprotection, goldfish, Carassius auratus
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The observation that hypoxia-induced KATP channel activation is
beneficial in mammals raises the possibility that a similar response in
aquatic ectotherms could promote tolerance of environmental hypoxia.
SarcKATP channel currents have been recorded in isolated myocytes
from the hearts of several teleost species
(Ganim et al., 1998;
Paajanen and Vornanen, 2002
),
and there is evidence for the existence of cardiac mitoKATP
channels in fish (MacCormack and Driedzic,
2002
). In addition, nitric oxide synthase (NOS) has been localized
in the hearts of goldfish (Bruning et al.,
1996
), and NO has been shown to play a critical role, via
cGMP, in regulating the heart and peripheral vasculature in a variety of
teleost species (Imbrogno et al.,
2003
; Jennings et al.,
2004
; Pellegrino et al.,
2003
). In goldfish, NO synthesized in cardiac myocytes plays a
role in sarcKATP channel activation during moderate hypoxia
(Cameron et al., 2003
).
Although it has been proposed that hypoxia-induced KATP channel
activation, whether in the heart or in the brain, contributes to the enhanced
tolerance of environmental oxygen depletion exhibited by many ectothermic
vertebrates (Cameron and Baghdady,
1994
; Pek-Scott and Lutz,
1998
), this possibility has not been directly tested in fish.
The purpose of the present study, then, was to determine whether
sarcKATP or mitoKATP channel activation exerts a
cardioprotective effect during hypoxia in goldfish. This species is highly
tolerant of depleted environmental oxygen; indeed, the congeneric crucian carp
Carassius carassius retains normal cardiac function for 5 days of
complete anoxia (Stecyk et al.,
2004). A cellular model of environmental hypoxia was used to
examine the effects of altered channel activity on isolated myocytes. Our
hypothesis was that the NO- and cGMP-dependent activation of cardiac
KATP channels would promote survival of isolated cells, thereby
contributing to a suite of mechanisms that dramatically enhance tolerance of
hypoxia in these fish. Preliminary results of this work have appeared in
abstract form (Zhu et al.,
2004
).
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Intracellular recording
Animals used for conventional intracellular recording ranged in size from
9.528.1 g (mean ± S.E.M.,
18.1±4.8 g). Procedures have been previously described
(Cameron et al., 2003);
briefly, the entire heart was mounted in a tissue bath and superfused with
normoxic saline solution at a rate of 15 ml min1. This
solution contained (in mmol l1) 150 NaCl, 5 KCl, 1.2
NaH2PO4, 1.2 MgSO4, 1.8 CaCl2, 10
Hepes and 10 glucose; pH was maintained at 7.6 and temperature held at
21±1°C.
Standard glass microelectrodes filled with 3 mol l1 KCl were connected to a differential amplifier (WPI, Sarasota, FL, USA), and spontaneous intracellular action potentials (APs) were recorded from the most superficial layer of ventricular muscle. APs were digitized (PowerLab; ADInstruments, Mountain View, CA USA) and analyzed using appropriate software (Chart, Peak Parameters; ADI). Parameters measured were action potential amplitude, resting membrane potential, slope of action potential upstroke phase and action potential duration at various levels of repolarization.
Oxygen partial pressure in the tissue bath was monitored using an oxygen meter (Cameron Instruments, Port Aransas, TX, USA) while moderate hypoxia (6.1±0.2 kPa) was induced by switching the superfusate from air-bubbled saline (20 kPa) to a glucose-free solution gassed with 100% N2. The new condition was reproducible, reversible, and achieved in the tissue bath within 1 min. Electrophysiological responses to the acute onset of hypoxia and to reoxygenation were first assessed in the absence of any drug. Recordings were collected after 1030 min exposure to hypoxia, and again 20 min after a return to normoxic solution.
Drugs
Drugs, including the nitric oxide (NO) donor
S-nitroso-N-acetylpenicillamine (SNAP; 100 µmol
l1), the nitric oxide synthase (NOS) inhibitor
N-Nitro-L-arginine methyl ester (L-NAME;
50 µmol l1), the KATP channel antagonist
glibenclamide (5 µmol l1), the mitoKATP
channel agonist 3-methyl-7-chloro-1,2,4-benzothiadiazine-1,1-dioxide
(diazoxide; 100 µmol l1), the stable and cell-permeable
cGMP analog 8-bromoguanosine 3':5'-cyclic monophosphate
(8-Br-cGMP; 100 µmol l1), and the mitoKATP
channel inhibitor 5-hydroxydecanoic acid (5-HD; 100 µmol
l1), were purchased from Sigma (St Louis, MO, USA).
Diazoxide was first dissolved in a drop of DMSO. Following the initial period
of equilibration in normoxic saline, the effects of SNAP, 8-Br-cGMP and
diazoxide on ventricular action potential parameters were recorded after 10
min exposure. In other experiments, glibenclamide or L-NAME was
made up in hypoxic solution and applied to the tissue bath as described above.
Dosages were chosen from among those recently employed in comparable
studies.
Cellular model of environmental hypoxia
Isolation of cardiac myocytes
Animals used for this procedure ranged in size from 23.7 to 64.9 g (mean
± S.E.M., 43.3±12.4 g). Cell
isolation procedures were modified from those of Karttunen and Tirri
(1986), as previously
described (Cameron et al.,
2003
). Upon removal, the heart was bathed in a chilled
Ca2+-containing saline buffer (µmol l1): 137
NaCl, 4.6 KCl, 3.5 NaH2PO4, 1.2 MgCl2, 11
glucose, 10 Hepes and 0.025 CaCl2. The atrium was tied off and an
olive-tipped cannula (27 gauge) was inserted into the ventricle through the
opening of the bulbus arteriosus. The ventricle was then perfused with an
identical but nominally Ca2+-free saline solution for 5 min,
followed by 25 minperfusion with an enzyme buffer containing 50 ml
Ca2+-free saline, 35 mg collagenase (Type I), 25 mg trypsin and 25
mg bovine serum albumin (Fraction V). The heart was removed from the perfusion
apparatus and carefully torn into small pieces. After 5 min of swirling
agitation followed by 5 min of gentle trituration with a Pasteur pipette, the
supernatant containing single free-floating cells was removed. Fresh buffer
was added, and the procedure repeated to obtain a second and third fraction of
cells. This procedure produced a high yield (8090%) of viable,
elongated myocytes.
Cellular model
The method used to assess cellular viability in hypoxia was derived from
the in vitro model of cellular ischemia developed by Vander Heide et
al. (1990), as modified by
Sato et al. (2000
). Portions
of the myocyte suspension (0.5 ml) were pipetted into 5 ml test tubes, and 0.5
ml of saline buffer or drug solution was added. The hypoxic condition was
induced in some tubes by layering an additional 0.5 ml of mineral oil on top
of the myocyte suspension, preventing gaseous diffusion of oxygen. After 60
min incubation, 0.5 ml of myocytes were sampled from each tube and mixed with
0.5 ml of staining solution containing 0.5% gluteraldehyde and 0.5% Trypan
Blue in saline buffer. The resulting ml of suspended cells was placed on a
slide and examined by phase contrast microscopy at 100x. Elongated
myocytes with a normal morphological appearance were included in the analysis,
while dead, `rounded-up' cells were excluded
(Vander Heide et al., 1990
).
These dead cells were always blue, and were presumed to have been damaged
during the enzymatic isolation procedure. Viability of the elongated cells was
assessed by their capacity to exclude Trypan Blue
(Fig. 1); the percentage
staining clearly after 3 min exposure to the staining solution was recorded
for each experimental condition. Myocytes staining dark blue were considered
irreversibly damaged. Drugs and concentrations were identical to those used in
the intracellular experiments; they were made up in saline buffer on the day
of an experiment and were present throughout the period of in vitro
hypoxia.
|
Data analysis
Data obtained from the intracellular and cellular hypoxia experiments were
transferred to Microsoft Excel spreadsheets; t-tests and analysis of
variance for repeated measures (ANOVA with post-hoc Fisher PLSD and
Scheffe F-test; Statview) were used to determine statistical
significance (P<0.05) among group means; results were expressed as
means ± S.E.M.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Glibenclamide and L-NAME in hypoxia
To examine the possibility that APD shortening in hypoxia was caused by the
activation of KATP channels, the effects of the channel antagonist
glibenclamide (5 µmol l1) on hypoxia-induced shortening
were monitored in isolated hearts. Simultaneous exposure to both glibenclamide
and hypoxia abolished the reduction in APD characteristic of hypoxia alone
(N=3; Fig. 3).
|
To determine whether NO plays a role in cellular responses to hypoxia in goldfish, the effects of the NOS inhibitor L-NAME were studied in isolated hearts and in ventricular myocytes. Hypoxia-induced shortening of APD90 was eliminated by previous exposure to 50 µmol l1 L-NAME (N=4; Fig. 3).
Effects of KATP activators under normoxic conditions
To determine whether NO and cGMP could mimic cellular responses to hypoxia,
the effects on action potential parameters of the NO donor SNAP and the stable
cGMP analog 8-Br-cGMP were monitored under normoxic conditions. At a
concentration of 100 µmol l1, SNAP significantly
(P<0.05) reduced APD90 after 10 min exposure
(N=4; Fig. 4). With
prolonged exposure to SNAP, APD was further reduced; at 60 min, both
APD50 and APD90 were significantly decreased. There were
no significant effects of SNAP on any other action potential parameter.
|
Cellular viability in vitro
A cellular model of environmental hypoxia was used to assess the potential
cardioprotective effects of KATP channel activation. Under normoxic
conditions, 37.8±4.0% of elongated, isolated ventricular myocytes from
goldfish were unable to exclude Trypan Blue, suggesting cellular injury
(N=6; Fig. 5). After
60 min hypoxia, however, the incidence of Trypan Blue-positive cells was
significantly (P<0.001) increased compared to that observed in
normoxia. The percentage of stained cells in hypoxia was 81.2±2.6, a
115% increase. More than 500 myocytes were individually evaluated.
|
Following simultaneous exposure of isolated myocytes to L-NAME and 60 min hypoxia, the percentage of Trypan Blue-stained cells was moderately increased relative to that seen with hypoxia alone (Fig. 6). After 60 min exposure of isolated myocytes to hypoxia plus SNAP, however, the percentage of Trypan Blue-stained cells was markedly reduced compared to that observed with hypoxia alone. To determine whether this cardioprotective action of SNAP was linked to the hypoxia-induced production of NO in muscle cells, the effect of SNAP in combination with L-NAME also was tested. Blockade of NO synthesis by L-NAME entirely eliminated the reduction in stained cells observed with SNAP and hypoxia alone (Fig. 6).
|
|
In mammals, diazoxide and 5-HD have been shown to be selective for
mitoKATP over sarcKATP channels the former as an
activator and the latter as an inhibitor
(Mannhold, 2004). In goldfish,
the beneficial effects of diazoxide in preserving isolated myocytes was
reduced, but not eliminated, by 5-HD (Fig.
7). In contrast, 5-HD did not alter the cardioprotective effect of
8-Br-cGMP; the reduction in the percentage of stained cells in hypoxia that
was produced by 8-Br-cGMP alone was not affected when this agent was given in
combination with the presumed mitoKATP blocker.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Electrophysiology
In the present study we confirm our previous observation
(Cameron et al., 2003) that
transmembrane action potential duration is significantly shortened during
moderate hypoxia in intact, isolated goldfish heart
(Fig. 2). In mammals, cardiac
APD shortening in hypoxia is thought to arise through the activation of
sarcKATP channels (Flagg et al.,
2004
; Shigematsu and Arita,
1997
; Suzuki et al.,
2002
). Patch clamp studies also have revealed a hypoxia-induced
increase in the activity of sarcKATP channels in both mammals
(Budas et al., 2004
;
Liu et al., 2001
) and goldfish
(Cameron et al., 2003
). We now
show that in fish, the APD shortening can be eliminated by simultaneous
exposure of the tissue glibenclamide (Fig.
3), an antagonist of both sarc- and mitoKATP channels.
The hypoxia-induced reduction in APD was also abolished by L-NAME,
an inhibitor of NO synthase, suggesting an upstream role for NO in the
activation of sarcKATP channels
(Fig. 3). Further, APD
shortening can be similarly induced by the NO donor SNAP, as well as by a
stable analog of cGMP (Fig. 4).
NO has previously been shown to activate sarcKATP channels in
mammalian cardiac muscle (Chen et al.,
2000
; Moncada et al.,
2000
), and this response has been linked to cGMP
(Chen et al., 2000
;
Han et al., 2001
). In
contrast, the mitoKATP activator diazoxide had no significant
effect on APD.
Cardioprotection in vitro
In an attempt to demonstrate that hypoxia-induced and NO-dependent
activation of KATP channels promotes the survival of ventricular
myocytes, we used an in vitro model of environmental hypoxia. Similar
methods have been used to simulate the effects of ischemia on isolated
mammalian cells, and to demonstrate, for example, the cardioprotective
activation of mitoKATP channels by diazoxide
(Sato et al., 2000) or
volatile anesthetics (Zaugg et al.,
2002
). In each study, the viability of apparently intact,
elongated myocytes was assessed by their capacity to exclude Trypan Blue
dye.
The present results indicate that ventricular myocytes from goldfish are
damaged after 60 min of in vitro hypoxia under mineral oil. As
illustrated in Fig. 5, cells
exposed to the low-oxygen environment were significantly more often positive
for Trypan Blue than those maintained under normoxic conditions. However, the
cellular damage caused by hypoxia could be reduced by agents thought to
activate KATP channels. Cells exposed to hypoxia in the presence of
SNAP or 8-Br-cGMP, both of which reduced APD in the intact heart, were much
more likely to survive and exclude the dye than were cells exposed to hypoxia
alone (Figs 6,
7). In contrast, the NOS
inhibitor L-NAME, which prevented hypoxia-induced APD shortening,
increased the numbers of stained, damaged cells. Perhaps surprisingly,
L-NAME also eliminated the cardioprotective influence of SNAP,
suggesting that SNAP promotes the endogenous synthesis and release of NO from
cardiac muscle cells. Confounding this analysis is the fact that hypoxia
itself may increase the NO concentration in cardiac muscle through activation
of NOS isoforms (which vary from one species to the next), or through
NOS-independent pathways (Schulz et al.,
2004). SNAP has been shown to increase the concentration of cGMP
in mammalian myocardium (Qin et al.,
2004
).
The present data strongly suggest that NO, in its capacity to activate
sarcKATP channels in goldfish, promotes survival of cardiac muscle
cells during hypoxia. The cardioprotective, cGMP- and
KATP-dependent influence of NO in hypoxia has been recently
reviewed (Kolar and Ostadal,
2004; Schulz et al.,
2004
). In mammalian myocytes, NOS is upregulated during ischemia
(Wang et al., 2002
), and a
similar enhancement of NOS activity occurs in response to hypoxia in the
vasculature of an elasmobranch fish
(Renshaw and Dyson, 1999
).
SarcKATP vs mitoKATP
While a cardioprotective role for KATP channel activation has
been described by many investigators, there remains some question as to the
relative roles of sarcolemmal vs mitochondrial channels
(Gross and Peart, 2003). In
the present study, the cellular damage induced by hypoxia could be reduced by
agents thought to specifically activate either sarcKATP or
mitoKATP channels. SNAP and 8-Br-cGMP, which reduce APD through
activation of sarcKATP channels, also promote tolerance of hypoxia
in isolated cells (Figs 6,
7). Diazoxide, which is thought
to act primarily at mitoKATP, also decreased the numbers of
stained, damaged myocytes (Fig.
7). In the present study, diazoxide did not affect APD
(Fig. 4), supporting the view
that its effect is primarily at the mitochondrial channel. However, a recent
study involving rat ventricular myocytes during metabolic inhibition indicates
that this agent can open sarcKATP channels as well, probably by an
indirect mechanism (Rodrigo et al.,
2004
). Finally, 5-HD, a specific inhibitor of mitoKATP
in mammals, was found to reduce (but not eliminate) the cardioprotective
influence of diazoxide, but to have no effect on the beneficial response to
8-Br-cGMP.
Data arising from mammalian studies of hypoxia and ischemic preconditioning
also suggest that activation of either sarcKATP or
mitoKATP channels can be cardioprotective
(Sanada et al., 2001;
Tanno et al., 2001
;
Toyoda et al., 2000
). Studies
of transgenic mice expressing a mutant KATP channel with reduced
ATP-sensitivity suggest that the sarcolemmal channel, at least in mammals, is
required for optimal response to ischemia
(Rajashree et al., 2002
). In
pharmacological studies, sarcKATP activation protects against
ischemic injury (Suzuki et al.,
2002
), and the present data suggest a similar action against
hypoxia in fish (Fig. 6). In
contrast, Sato et al. used an in vitro model of cellular ischemia,
very similar to that employed in the present study, to show that activation of
mitoKATP channels, and not sarcKATP channels, was
responsible for ischemic cardioprotection in rabbit myocytes
(Sato et al., 2000
). Indeed,
many recent studies, most involving diazoxide, 5-HD and other agents presumed
to be selective for cardiac sarcKATP vs
mitoKATP channels, implicate the latter subtype in protection
against ischemia (Murata et al.,
2001
; Oldenburg et al.,
2002
; Uchiyama et al.,
2003
).
There has been considerable speculation as to the specific benefits
provided to the myocardium by sarcKATP or mitoKATP
channel activation (Gross and Fryer,
1999; Oldenburg et al.,
2002
). Recent evidence suggests that NO/cGMP-dependent
cardioprotection involves mitoKATP channels, not as an
end-effector, but as an element in a cascade of events leading to the
production of reactive oxygen species (ROS;
Lebuffe et al., 2003
;
Qin et al., 2004
;
Xu et al., 2004
).
One factor that hinders the interpretation of data in studies such as these
is that many of the pharmacological agents typically used, including several
of those employed in the present study, may protect the heart by means
unrelated to ion channel activation. It has been reported that the
cardioprotective influence of SNAP, for example, may involve the mitochondria
and be unrelated to its capacity to affect sarcKATP channels
(Rakhit et al., 2001). Both
diazoxide and 5-HD can have beneficial but channel-independent effects on
mitochondrial metabolism (Dzeja et al.,
2003
; Hanley et al.,
2002
), leading at least one group to challenge the existence of
diazoxide- and 5-HD-sensitive KATP channels in mammalian
mitochondria (Das et al.,
2003
). In addition, preliminary data from our laboratory suggest
that 5-HD eliminates the reduction in APD characteristic of hypoxia,
suggesting that this agent is not specific to mitoKATP channels in
fish, or that other channels are affected. The present data cannot exclude the
possibility that diazoxide benefits goldfish myocytes by means other than
mitoKATP channel activation. This could underlie our observation
that 5-HD reduced, but did not completely eliminate, the cardioprotective
effects of diazoxide (Fig.
7).
It is now widely accepted that the NO- and cGMP-dependent activation of
sarcKATP and/or mitoKATP channels is cardioprotective
under conditions of metabolic stress in mammals, and that channel activity
underlies the phenomenon of ischemic preconditioning
(Gross and Peart, 2003;
Kolar and Ostadal, 2004
).
Aquatic ectotherms may be regularly exposed to acute or chronic environmental
hypoxia. Moreover, both sarcKATP
(Cameron et al., 2003
;
Paajanen and Vornanen, 2002
)
and mitoKATP (MacCormack and
Driedzic, 2002
; MacCormack et
al., 2003
) channels exist in the hearts of teleost fish, and the
former are specifically activated in hypoxia by a NO-dependent mechanism
(Cameron et al., 2003
). The
present findings support the hypothesis that sarcKATP or
mitoKATP channel activation promotes the survival of ventricular
myocytes exposed to conditions of depleted oxygen in vitro. A similar
channel activation in critical tissues in vivo may extend
whole-animal tolerance of hypoxia.
![]() |
Acknowledgments |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Bruning, G., Hattwig, K. and Mayer, B. (1996). Nitric oxide synthase in the peripheral nervous system of the goldfish, Carassius auratus. Cell Tissue Res. 284, 87-98.[CrossRef][Medline]
Budas, G. R., Jovanovic, S., Crawford, R. M. and Jovanovic,
A. (2004). Hypoxia-induced preconditioning in adult
stimulated cardiomyocytes is mediated by the opening and trafficking of
sarcolemmal KATP channels. FASEB J.
18,1046
-1048.
Cameron, J. S. and Baghdady, R. (1994). Role of ATP sensitive potassium channels in long term adaptation to metabolic stress. Cardiovasc. Res. 28,788 -796.[Medline]
Cameron, J. S., Hoffmann, K. E., Zia, C., Hemmett, H. M.,
Kronsteiner, A. and Lee, C. M. (2003). A role for
nitric oxide in hypoxia-induced activation of cardiac KATP channels
in goldfish (Carassius auratus). J. Exp.
Biol. 206,4057
-4065.
Chen, C. C., Lin, Y. C., Chen, S. A., Luk, H. N., Ding, P. Y., Chang, M. S. and Chiang, C. E. (2000). Shortening of cardiac action potentials in endotoxic shock in guinea pigs is caused by an increase in nitric oxide activity and activation of the adenosine triphosphate-sensitive potassium channel. Crit. Care Med. 28,1713 -1720.[CrossRef][Medline]
Das, M., Parker, J. E. and Halestrap, A. P.
(2003). Matrix volume measurements challenge the existence of
diazoxide/glibencamide-sensitive KATP channels in rat mitochondria.
J. Physiol. 547,893
-902.
Dawn, B. and Bolli, R. (2002). Role of nitric
oxide in myocardial preconditioning. Ann. NY Acad.
Sci. 962,18
-41.
Dzeja, P. P., Bast, P., Ozcan, C., Valverde, A., Holmuhamedov, E. L., Van Wylen, D. G. and Terzic, A. (2003). Targeting nucleotide-requiring enzymes: implications for diazoxide-induced cardioprotection. Am. J. Physiol. 284,H1048 -H1056.
Flagg, T. P., Charpentier, F., Manning-Fox, J., Remedi, M. S., Enkvetchakul, D., Lopatin, A., Koster, J. and Nichols, C. (2004). Remodeling of excitation-contraction coupling in transgenic mice expressing ATP-insensitive sarcolemmal KATP channels. Am. J. Physiol. 286,H1361 -H1369.
Ganim, R. B., Peckol, E. L., Larkin, J., Ruchhoeft, M. L. and Cameron, J. S. (1998). ATP-sensitive K+ channels in cardiac muscle from cold-acclimated goldfish: characterization and altered response to ATP. Comp. Biochem. Physiol. 119A,395 -401.
Gross, G. J. and Fryer, R. M. (1999).
Sarcolemmal versus mitochondrial ATP-sensitive K+ channels and
myocardial preconditioning. Circ. Res.
84,973
-979.
Gross, G. J. and Peart, J. N. (2003). KATP channels and myocardial preconditioning: an update. Am. J. Physiol. 285,H921 -H930.
Grover, G. J. and Garlid, K. D. (2000). ATP-sensitive potassium channels: a review of their cardioprotective pharmacology. J. Mol. Cell. Cardiol. 32,677 -695.[CrossRef][Medline]
Han, J., Kim, N., Kim, E., Ho, W. and Earm, Y. E.
(2001). Modulation of ATP-sensitive potassium channels by
cGMP-dependent protein kinase in rabbit ventricular myocytes. J.
Biol. Chem. 276,22140
-22147.
Hanley, P. J., Mickel, M., Loffler, M., Brandt, U. and Daut,
J. (2002). KATP channel-independent targets of
diazoxide and 5-hydroxydecanoate in the heart. J.
Physiol. 542,735
-741.
Imbrogno, S., Cerra, M. C. and Tota, B. (2003).
Angiotensin II-induced inotropism requires an endocardial endothelium-nitric
oxide mechanism in the in-vitro heart of Anguilla anguilla. J. Exp.
Biol. 206,2675
-2684.
Inoue, I., Nagase, H., Kishi, K. and Higuti, T. (1991). ATP-sensitive K+ channel in the mitochondrial inner membrane. Nature 352,244 -247.[CrossRef][Medline]
Jennings, B. L., Broughton, B. R. and Donald, J. A.
(2004). Nitric oxide control of the dorsal aorta and the
intestinal vein of the Australian short-finned eel Anguilla australis.J. Exp. Biol. 207,1295
-1303.
Karttunen, P. and Tirri, R. (1986). Isolation and characterization of single myocardial cells from the perch, Perca fluviatilis. Comp. Biochem. Physiol. 84A,181 -188.[CrossRef]
Kolar, F. and Ostadal, B. (2004). Molecular mechanisms of cardiac protection by adaptation to chronic hypoxia. Physiol. Res. 53,S3 -S13.[Medline]
Lebuffe, G., Schumacker, P. T., Shao, Z. H., Anderson, T., Iwase, H. and Vanden Hoek, T. L. (2003). ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel. Am. J. Physiol. 284,H299 -H308.
Liu, H., Chen, H., Yang, X. and Cheng, J. (2001). ATP sensitive K+ channel may be involved in the protective effects of preconditioning in isolated guinea pig cardiomyocytes. Chin. Med. J. (Engl.) 114,178 -182.[Medline]
MacCormack, T. J. and Driedzic, W. R. (2002).
Mitochondrial ATP-sensitive K+ channels influence force development
and anoxic contractility in a flatfish, yellowtail flounder Limanda
ferruginea, but not Atlantic cod Gadus morhua heart.
J. Exp. Biol. 205,1411
-1418.
MacCormack, T. J., Treberg, J. R., Almeida-Val, V. M., Val, A. L. and Driedzic, W. R. (2003). Mitochondrial KATP channels and sarcoplasmic reticulum influence cardiac force development under anoxia in the Amazonian armored catfish Liposarcus pardalis. Comp. Biochem. Physiol. 134A,441 -448.
Mannhold, R. (2004). KATP channel openers: structure-activity relationships and therapeutic potential. Med. Res. Rev. 24,213 -266.[CrossRef][Medline]
Moncada, G. A., Kishi, Y., Numano, F., Hiraoka, M. and Sawanobori, T. (2000). Effects of acidosis and NO on nicorandil-activated KATP channels in guinea-pig ventricular myocytes. Br. J. Pharmacol. 131,1097 -1104.[CrossRef][Medline]
Murata, M., Akao, M., O'Rourke, B. and Marban, E.
(2001). Mitochondrial ATP-sensitive potassium channels attenuate
matrix Ca2+ overload during simulated ischemia and reperfusion:
possible mechanism of cardioprotection. Circ. Res.
89,891
-898.
Noma, A. (1983). ATP-regulated K channels in cardiac muscle. Nature 305,147 -148.[CrossRef][Medline]
O'Rourke, B. (2000). Myocardial KATP
channels in preconditioning. Circ. Res.
87,845
-855.
Oldenburg, O., Cohen, M. V., Yellon, D. M. and Downey, J. M. (2002). Mitochondrial KATP channels: role in cardioprotection. Cardiovasc. Res. 55,429 -437.[CrossRef][Medline]
Paajanen, V. and Vornanen, M. (2002). The induction of an ATP-sensitive K+ current in cardiac myocytes of air- and water-breathing vertebrates. Pflügers Arch. 444,760 -770.[CrossRef][Medline]
Pek-Scott, M. and Lutz, P. L. (1998). ATP-sensitive K+ channel activation provides transient protection to the anoxic turtle brain. Am. J. Physiol. 275,R2023 -R2027.[Medline]
Pellegrino, D., Acierno, R. and Tota, B. (2003). Control of cardiovascular function in the icefish Chionodraco hamatus: involvement of serotonin and nitric oxide. Comp. Biochem. Physiol. 134A,471 -480.
Qin, Q., Yang, X. M., Cui, L., Critz, S. D., Cohen, M. V., Browner, N., Lincoln, T. M. and Downey, J. M. (2004). Exogenous nitric oxide triggers preconditioning by a cGMP- and mKATP-dependent mechanism. Am. J. Physiol. 287,H712 -H718.
Rajashree, R., Koster, J. C., Markova, K. P., Nichols, C. G. and Hofmann, P. A. (2002). Contractility and ischemic response of hearts from transgenic mice with altered sarcolemmal KATP channels. Am. J. Physiol. 283,H584 -H590.
Rakhit, R. D., Mojet, M. H., Marber, M. S. and Duchen, M. R.
(2001). Mitochondria as targets for nitric oxide-induced
protection during simulated ischemia and reoxygenation in isolated neonatal
cardiomyocytes. Circulation
103,2617
-2623.
Renshaw, G. M. and Dyson, S. E. (1999). Increased nitric oxide synthase in the vasculature of the epaulette shark brain following hypoxia. NeuroRep. 10,1707 -1712.
Rodrigo, G. C., Davies, N. W. and Standen, N. B. (2004). Diazoxide causes early activation of cardiac sarcolemmal KATP channels during metabolic inhibition by an indirect mechanism. Cardiovasc. Res. 61,570 -579.[CrossRef][Medline]
Sanada, S., Kitakaze, M., Asanuma, H., Harada, K., Ogita, H., Node, K., Takashima, S., Sakata, Y., Asakura, M., Shinozaki, Y. et al. (2001). Role of mitochondrial and sarcolemmal KATP channels in ischemic preconditioning of the canine heart. Am. J. Physiol. 280,H256 -H263.
Sato, T., Sasaki, N., Seharaseyon, J., O'Rourke, B. and Marban,
E. (2000). Selective pharmacological agents implicate
mitochondrial but not sarcolemmal KATP channels in ischemic
cardioprotection. Circulation
101,2418
-2423.
Schulz, R., Kelm, M. and Heusch, G. (2004). Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovasc. Res. 61,402 -413.[CrossRef][Medline]
Shigematsu, S. and Arita, M. (1997). Anoxia-induced activation of ATP-sensitive K+ channels in guinea pig ventricular cells and its modulation by glycolysis. Cardiovasc. Res. 35,273 -282.[CrossRef][Medline]
Stecyk, J. A., Stenslokken, K. O., Farrell, A. P. and Nilsson,
G. E. (2004). Maintained cardiac pumping in anoxic crucian
carp. Science 306,77
.
Suzuki, M., Sasaki, N., Miki, T., Sakamoto, N., Ohmoto-Sekine,
Y., Tamagawa, M., Seino, S., Marban, E. and Nakaya, H.
(2002). Role of sarcolemmal KATP channels in
cardioprotection against ischemia/reperfusion injury in mice. J.
Clin. Invest. 109,509
-516.
Tanno, M., Miura, T., Tsuchida, A., Miki, T., Nishino, Y., Ohnuma, Y. and Shimamoto, K. (2001). Contribution of both the sarcolemmal KATP and mitochondrial KATP channels to infarct size limitation by KATP channel openers: differences from preconditioning in the role of sarcolemmal KATP channels. Naunyn Schmiedebergs Arch. Pharmacol. 364,226 -232.[CrossRef][Medline]
Toyoda, Y., Friehs, I., Parker, R. A., Levitsky, S. and McCully, J. D. (2000). Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning. Am. J. Physiol. 279,H2694 -H2703.
Uchiyama, Y., Otani, H., Wakeno, M., Okada, T., Uchiyama, T., Sumida, T., Kido, M., Imamura, H., Nakao, S. and Shingu, K. (2003). Role of mitochondrial KATP channels and protein kinase C in ischaemic preconditioning. Clin. Exp. Pharmacol. Physiol. 30,426 -436.[CrossRef][Medline]
Vander Heide, R. S., Rim, D., Hohl, C. M. and Ganote, C. E. (1990). An in vitro model of myocardial ischemia utilizing isolated adult rat myocytes. J. Mol. Cell. Cardiol. 22,165 -181.[CrossRef][Medline]
Wang, Y., Kudo, M., Xu, M., Ayub, A. and Ashraf, M. (2001). Mitochondrial KATP channel as an end effector of cardioprotection during late preconditioning: triggering role of nitric oxide. J. Mol. Cell. Cardiol. 33,2037 -2046.[CrossRef][Medline]
Wang, Y., Guo, Y., Zhang, S. X., Wu, W. J., Wang, J., Bao, W. and Bolli, R. (2002). Ischemic preconditioning upregulates inducible nitric oxide synthase in cardiac myocyte. J. Mol. Cell. Cardiol. 34,5 -15.[CrossRef][Medline]
Xu, Z., Ji, X. and Boysen, P. G. (2004). Exogenous nitric oxide generates ROS and induces cardioprotection: involvement of PKG, mitochondrial KATP channels, and ERK. Am. J. Physiol. 286,H1433 -H1440.
Zaugg, M., Lucchinetti, E., Spahn, D. R., Pasch, T. and Schaub, M. C. (2002). Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial KATP channels via multiple signaling pathways. Anesthesiol. 97,4 -14.[CrossRef][Medline]
Zhu, J., Wilson, I., Gannon, J. M. and Cameron, J. S. (2004). Cardioprotective activation of cardiac KATP channels during hypoxia in goldfish (Abstr.). FASEB J. 18, A367.