1Department of Anatomy, Physiology, and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, Alabama 36849; and 2Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida 32306
Submitted 2 December 2003 ; accepted in final form 29 March 2004
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
cell swelling; protein kinases; calcium current
The cellular and molecular mechanisms that link changes in cell volume to the activation of different ion channels remain of great interest. In guinea pig cardiac myocytes and canine pulmonary arterial smooth muscle cells, cell swelling-induced activation of Cl channels is thought to result from inhibition of protein kinase C (PKC) or enhancement of phosphatase (8, 42). In rabbit pulmonary arterial myocytes, activation of Ca2+-activated K+ channels appears to occur by a direct effect of stretch on the channels (18). Modulation of L-type Ca2+ channels in rabbit cardiac cells by osmotic cell swelling and by cell inflation via the patch pipette was dependent neither on protein kinase A (PKA) nor on intracellular Ca2+ (22). L-type Ca2+ current in smooth muscle cells of the human stomach is also enhanced by hypotonic cell swelling, but the mechanism is not clear (17).
The purpose of the present study was to delineate the mechanism underlying the effect of hypotonic cell swelling on L-type Ca2+ channels in rabbit portal vein smooth muscle cells. Using the conventional whole cell technique and various protein kinase activators and inhibitors, we have demonstrated that exposure of cells to a hypotonic bath solution significantly increases L-type Ca2+ channel activity. Furthermore, PKC appears to play an important role in the hypotonic swelling-induced activation of these channels.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Electrophysiology.
Inward Ba2+ current (IBa) in vascular myocytes was measured with the whole cell patch-clamp technique at room temperature (40). A drop of cell suspension was added to a small recording chamber mounted on the stage of an inverted microscope (Nikon TS-100). Cells in the chamber were superfused by gravity at a constant rate (12 ml/min). Patch electrodes were made from borosilicate glass pulled with a micropipette puller (PP-830, Narishige) and fire-polished with a microforge (MF-830, Narishige). Pipette resistance was 35 M
when filled with the appropriate solution. After the whole cell configuration was established, membrane capacitance and series resistance were recorded with a 20-mV hyperpolarization potential and were partially compensated. Inward current was elicited by stepping voltage from the holding potential of 70 mV to 0 mV at 30-s intervals with an Axopatch 200B patch-clamp amplifier and pCLAMP 8 (Axon Instruments). The leak currents at both isotonic and hypotonic states were not subtracted. The standard isotonic bath solution (
290 mosmol/kgH2O) used to record inward IBa in portal vein cells was composed of (in mM) 80 NaCl, 10 tetraethylammonium chloride (TEA-Cl), 5 BaCl2, 0.5 MgCl2, 5.5 glucose, 5 CsCl, 10 HEPES, and 70 D-mannitol, pH 7.40 with NaOH. Both TEA-Cl and CsCl were used to block K+ currents. The standard hypotonic solution was made from the isotonic bath solution by removing D-mannitol (
220 mosmol/kgH2O). The standard hypertonic bath solution was made from the isotonic solution by adding 70 mM D-mannitol (total D-mannitol 140 mM,
360 mosmol/kgH2O). The pipette solution contained (in mM) 80 CsCl, 20 TEA-Cl, 5 glucose, 2 MgCl2, 5 ATP, 1 GTP, 5 EGTA, and 80 D-mannitol, pH 7.2 with CsOH (40).
PKC- mRNA expression.
RT-PCR was used to evaluate the expression of PKC-
mRNA. Total RNA was isolated by a monophasic solution of phenol and guanidine isothiocyanate with TRIzol according to the manufacturer's instructions (Life Technologies, Grand Island, NY). Rabbit portal vein smooth muscle rings were homogenized in TRIzol. Phase separation was carried out with chloroform (0.2 ml chloroform/ml TRIzol) and centrifuged at 12,000 g for 15 min at 4°C. The aqueous phase was removed, and the RNA was precipitated with isopropanol and washed two times with 75% ethanol. The RNA was resolved in diethyl pyrocarbonate-treated water. RNA concentration was measured spectrophotometrically at 260 nm.
One-step RT-PCR was performed with the cMaster RTplus PCR System (Eppendorf, Westbury, NY). Total RNA (0.5 µg) was incubated with RTplus PCR buffer containing Mg2+ (2.5 mM), dNTPs (200 µM each), cMaster RT enzyme (0.15 U/µl), cMaster PCR enzyme (0.05 U/µl) and PKC- forward and reverse primers (400 nM) in a total volume of 20 µl. The PCR primer sequences were PKC-
(forward) 5'-GCTCTGGCGCGGAAACACCCTTAT-3' and PKC-
(reverse) 5'-GATGGCTGGGCAGCCTCCCTTT-3'. Primers were derived from the human PKC-
gene (GenBank accession no. NM005400) and produced an amplification product of 440 bp. Control reactions were performed in the absence of RT. RT-PCR was carried out in a Bio-Rad iCycler. The RT step was performed at 50°C for 45 min. The PCR reaction was carried out 94°C for 2 min followed by 35 cycles of 94°C for 15 s, 60°C for 30 s, and 68°C for 45 s. Primer extension was carried out at 68°C for 3 min. RT-PCR amplification products were analyzed on a 1.2% agarose gel and stained with ethidium bromide. The gels were visualized by ultraviolet light and photographed with a Bio-Rad Fluor S MultiImager. To confirm the identity of the PCR product, the band was cut out and eluted with the PerfectPrep Gel Cleanup Kit (Eppendorf) and TA cloned into pCR2.1 with the Original TA Cloning Kit (Invitrogen, Carlsbad, CA). One Shot chemically competent cells (INV
F'; Invitrogen) were transformed, and plasmid DNA was isolated for sequencing. Sequencing was performed at the Auburn University Genomic and Sequencing Laboratory.
Drugs and reagents.
PDBu, Ro-31-8425, Go-6983, and KT-5720 were purchased from Calbiochem (La Jolla, CA). Isoproterenol, nicardipine, niflumic acid, and DIDS were purchased from Sigma. Those drugs not soluble in water were first dissolved in dimethyl sulfoxide (DMSO) and then further diluted in the appropriate solution with the final concentration of DMSO <0.2%. DMSO alone at 0.2% had no effect on Ca2+ currents. The PKC translocation inhibitory peptides C2-4 (SLNPEWNET, corresponding to residues 218226 of PKC-
),
V1-2 (EAVSLKPT, corresponding to residues 1421 of PKC-
), and scrambled
V1-2 (LSETKPAV) were purchased from Calbiochem.
Statistical analysis. Values are reported as means ± SE, and n is the number of cells studied. Single-point data between control and treated cells were compared with the two-tailed unpaired Student's t-test. Comparisons between multiple groups were done with a two-way ANOVA with a Student-Newman-Kuels posttest. P values <0.05 were considered significantly different.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
To examine the effect of hypotonic cell swelling on the voltage-dependent characteristics of L-type Ca2+ channels, we compared the current-voltage (I-V) relationships and the steady-state inactivation under isotonic and hypotonic conditions. The I-V relationship was measured when the test membrane potentials were stepped between 60 and +60 mV by increments of 10 mV from the holding potential of 70 mV in the presence of either DIDS or niflumic acid. As shown in Fig. 3A, peak IBa was significantly higher at test potentials between 40 and +30 mV after hypotonic exposure in the presence of DIDS. The test potentials for threshold current and the maximal peak current were also shifted toward the left after hypotonic exposure in the presence of DIDS. Similarly, exposure of cells to hypotonic solution significantly increased the peak currents at the test potentials between 30 and + 30 mV in the presence of niflumic acid. However, hypotonic exposure did not change the voltage-dependent patterns of the current in this group of experiments (Fig. 3B). The left shift of the I-V relationship by hypotonic exposure in the first set of experiments suggested possible contamination of IBa by ICl-swell at the negative test potentials in the presence of DIDS, as DIDS is more potent to block ICl-swell at positive membrane potentials (13). On the other hand, niflumic acid has been reported to be equally potent in blocking ICl-swell at all membrane potentials (13). Our data suggest that hypotonic exposure did not change the shape of the I-V relationship, whereas it significantly enhanced IBa at most test potentials.
|
PKC plays an important role in hypotonic swelling-induced activation of Ca2+ channels.
In vascular smooth muscle cells, both PKA and PKC are able to stimulate L-type Ca2+ channels, whereas protein kinase G (PKG) has an inhibitory effect (for review, see Ref. 16). To examine the mechanism underlying the hypotonic swelling-induced stimulation of Ca2+ channel activity in vascular smooth muscle cells, we first tested whether PKA plays a role in the signal transduction pathway. Cells were treated with a specific PKA inhibitor, KT-5720, before and during exposure to hypotonic solution. A previous report (41) indicated that KT-5720 has no detectable effect on basal Ca2+ channel currents but eliminated the stimulatory effect of PKA in rabbit portal vein smooth muscle cells. Figure 4A indicates that at the maximal concentration needed to inhibit PKA activity KT-5720 (200 nM) did not prevent the increase of IBa induced by hypotonic exposure. The increases in IBa induced by hypotonic exposure were 31 ± 3% and 29 ± 4%, respectively, in the absence (n = 16) and presence (n = 11) of KT-5720. In another group of experiments, effects of the -adrenergic receptor agonist isoproterenol (Iso) on IBa were examined after cell exposure to hypotonic solution. As shown in Fig. 4B, exposure to hypotonic solution increased peak IBa
30%. Application of Iso (1 µM) under hypotonic conditions further increased peak IBa by 30%. Peak IBa in response to hypotonic exposure plus Iso was 158 ± 7% of that under isotonic conditions without Iso treatment (n = 8). When these experiments were repeated in the presence of KT-5720, exposure of cells to hypotonic solution significantly increased peak IBa. However, the stimulatory effect of Iso on IBa under hypotonic condition was completely prevented (Fig. 4C; n = 7). These data suggest that PKA is not involved in the cell swelling-induced increase of IBa.
|
|
Involvement of PKC in the hypotonic swelling-induced stimulation of IBa was further evaluated with the PKC activator PDBu (200 nM). Application of PDBu under isotonic conditions significantly increased IBa, which reached a steady state in 5 min. Switching the superfusate from isotonic to hypotonic solution in the presence of PDBu did not further change the amplitude of inward current (Fig. 6, A and B). In another set of experiments, cells were treated with PDBu after hypotonic exposure. Again, peak IBa was significantly increased when cells were exposed to hypotonic solution. Application of PDBu under hypotonic conditions did not further increase Ca2+ channel activity (Fig. 6, C and D).
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Hypotonicity of the extracellular environment occurs in several situations including reduced extracellular Na+ concentration seen in normal pregnancy (11), overhydration following intense exercise (1, 12), and treatment with citalopram (15). Other hyposmotic states are found in situations involving deficits in plasma proteins secondary to hepatic dysfunction and nutritional deficits. L-type Ca2+ channels play a central role in the excitation-contraction coupling in vascular smooth muscle cells, and it has been suggested that activation of L-type Ca2+ channels is responsible for the vasoconstriction induced by osmotic swelling (2). Ca2+ channels are also activated by membrane depolarization through volume-regulated Cl channels or stretch-activated nonselective cation channels (4, 19, 23, 26, 37). Our data demonstrated a proportional increase in peak IBa in response to gradual reductions in osmolality. These data are consistent with the reports that graded decreases of extracellular osmolarity lead to a proportional increase in the tension of guinea pig aortic strips (19) and rat portal vein rings (2). Our data are also consistent with other reports demonstrating that L-type Ca2+ channels in vascular smooth muscle cells are stimulated by inflating cells with positive pressure through a pipette electrode (4, 20, 23). Thus activation of Ca2+ channels may play an important role in the myogenic response under physiological and pathophysiological conditions. Although the 25% reduction of extracellular osmolarity used in this study may not occur under normal physiological conditions, it has been used as a common experimental procedure for the study of volume-regulated channels by many research groups (5, 13, 21, 37, 42).
Previous studies on various volume-regulated anion channels in different cell types demonstrated that PKA activation plays an important role in the cell volume change-induced modulation of these channels (14, 6, 10, 34). In the present study, we evaluated the possible involvement of PKA in the modulation of L-type Ca2+ channels in vascular smooth muscle cells by hypotonic cell swelling. Exposure of cells to hypotonic bath solution did not prevent, but rather blunted, the stimulatory effects of Iso on IBa. In addition, pretreatment of cells with the PKA inhibitor KT-5720 did not prevent the increase in IBa induced by hypotonic swelling but prevented further increase of IBa by Iso under hypotonic conditions. These data are consistent with previous reports that Iso induces a >50% increase in Ca2+ channel currents in both rabbit and rat portal vein smooth muscle cells through activation of both PKA and PKC (36, 41). Thus it is unlikely that hypotonic swelling stimulates Ca2+ channel activity through activation of PKA in vascular smooth muscle cells.
Modulation of volume-regulated ion channels by PKC has also been reported. For example, PKC inhibitors enhanced the basal ICl-swell under isotonic conditions and further abolished the swelling-induced activation of ICl-swell in canine pulmonary artery smooth muscle cells (42) and guinea pig cardiac myocytes (8). In contrast, phorbol esters dose-dependently increased the amplitude of ICl-swell in canine atrial myocytes (7). More pertinent to our study is a recent report demonstrating that in rabbit portal vein smooth muscle cells phorbol esters increased, whereas PKC inhibitors decreased, the amplitude of ICl-swell (10). Thus hypotonic swelling may activate ICl-swell through activation (7, 10) or inhibition (8, 42) of PKC in different cells. The discrepancy in the PKC-dependent modulation of ICl-swell might be related to species variation. In the present study, stimulation of endogenous PKC by PDBu strongly increased peak IBa under isotonic conditions and prevented further current enhancement by hypotonic swelling, whereas PKC inhibitors completely abolished IBa stimulation by hypotonic cell swelling. Long-term treatment of cells with PDBu to downregulate endogenous PKC activity also abolished IBa stimulation induced by hypotonic cell swelling. These data strongly suggest that a hypotonic-induced cell volume change can stimulate L-type Ca2+ channels by activating PKC in rabbit portal vein cells. Furthermore, our results demonstrated that the selective inhibitory peptide against PKC-,
V1-2, was able to prevent the activation of Ca2+ channels by hypotonic swelling, whereas neither the scrambled
V1-2 nor the selective conventional PKC inhibitor
C2-4 was effective. Thus PKC-
may play an important role in the hypotonic swelling-induced activation of Ca2+ channels.
Although our results do not directly answer the question as to how cell swelling stimulates PKC activity in this cell type, results from other groups have demonstrated a PKC isozyme-specific interaction with F-actin (29, 30) and caveolae (27, 32). In addition, possible redistribution or reorganization of F-actin and caveolar microdomains during cell swelling has been suggested (25, 28). If F-actin and caveolin serve as essential anchoring proteins for specific PKC isozymes, alteration of F-actin or caveolin during cell swelling may change PKC translocation and activity to its specific targets. Whether this same mechanism can account for cell swelling-induced stimulation of L-type Ca2+ channels in rabbit portal vein smooth muscle cells has not yet been elucidated and deserves further study. In addition, further studies should also answer the question of whether the cell swelling-induced increase of IBa through these channels is related to the increase of single-channel conductance, open channel probability, or number of functional channels.
In summary, results from the present study demonstrate for the first time that hypotonic cell swelling can enhance L-type Ca2+ channel activity in rabbit portal vein smooth muscle cells. Furthermore, PKC, but not PKA, plays an important role in the cell swelling-induced stimulation of L-type Ca2+ channels. Thus stimulation of Ca2+ channels as well as stimulation of volume-regulated Cl channels by hypotonic cell swelling may subsequently enhance the contractility of blood vessels and be a mechanism for modulating afterload in arteriolar vessels or preload (capacitance) in venous vessels.
![]() |
GRANTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
FOOTNOTES |
---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2. Bulow A and Johansson B. Membrane stretch evoked by cell swelling increases contractile activity in vascular smooth muscle through dihydropyridine-sensitive pathways. Acta Physiol Scand 152: 419427, 1994.[ISI][Medline]
3. Clement-Chomienne O, Walsh MP, and Cole WC. Angiotensin II activation of protein kinase C decreases delayed rectifier K+ current in rabbit vascular myocytes. J Physiol 495: 689700, 1996.[Abstract]
4. Davis MJ, Donovitz JA, and Hood JD. Stretch-activated single-channel and whole cell currents in vascular smooth muscle cells. Am J Physiol Cell Physiol 262: C1083C1088, 1992.
5. Decher N, Lang HJ, Nilius B, Bruggemann A, Busch AE, and Steinmeyer K. DCPIB is a novel selective blocker of ICl,swell and prevents swelling-induced shortening of guinea-pig atrial action potential duration. Br J Pharmacol 134: 14671479, 2001.
6. Du XY and Sorota S. Modulation of dog atrial swelling-induced chloride current by cAMP: protein kinase A-dependent and -independent pathways. J Physiol 500: 111122, 1997.[Abstract]
7. Du XY and Sorota S. Protein kinase C stimulates swelling-induced chloride current in canine atrial cells. Pflügers Arch 437: 227234, 1999.[CrossRef][ISI][Medline]
8. Duan D, Cowley S, Horowitz B, and Hume JR. A serine residue in ClC-3 links phosphorylation-dephosphorylation to chloride channel regulation by cell volume. J Gen Physiol 113: 5770, 1999.
9. Duan D, Hume JR, and Nattel S. Evidence that outwardly rectifying Cl channels underlie volume-regulated Cl currents in heart. Circ Res 80: 103113, 1997.
10. Ellershaw DC, Greenwood IA, and Large WA. Modulation of volume-sensitive chloride current by noradrenaline in rabbit portal vein myocytes. J Physiol 542: 537547, 2002.
11. Ezimokhai M and Osman N. The effect of sodium based hypo-osmolality on arterial smooth muscle reactivity in vitro. Res Exp Med (Berl) 197: 269279, 1998.[CrossRef][Medline]
12. Gardner JW. Death by water intoxication. Mil Med 167: 432434, 2002.[ISI][Medline]
13. Greenwood IA and Large WA. Properties of a Cl current activated by cell swelling in rabbit portal vein vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 275: H1524H1532, 1998.
14. Hall SK, Zhang J, and Lieberman M. Cyclic AMP prevents activation of a swelling-induced chloride-sensitive conductance in chick heart cells. J Physiol 488: 359369, 1995.[Abstract]
15. Hull M, Kottlors M, and Braune S. Prolonged coma caused by low sodium and hypo-osmolarity during treatment with citalopram. J Clin Psychopharmacol 22: 337338, 2002.[CrossRef][ISI][Medline]
16. Keef KD, Hume JR, and Zhong J. Regulation of cardiac and smooth muscle Ca2+ channels (CaV1.2a,b) by protein kinases. Am J Physiol Cell Physiol 281: C1743C1756, 2001.
17. Kim CH, Rhee PL, Rhee JC, Kim YI, So I, Kim KW, Park MK, Uhm DY, and Kang TM. Hypotonic swelling increases L-type calcium current in smooth muscle cells of the human stomach. Exp Physiol 85: 497504, 2000.[Abstract]
18. Kirber MT, Ordway RW, Clapp LH, Walsh JV Jr, and Singer JJ. Both membrane stretch and fatty acids directly activate large conductance Ca2+-activated K+ channels in vascular smooth muscle cells. FEBS Lett 297: 2428, 1992.[CrossRef][ISI][Medline]
19. Lang F, Busch GL, Zempel G, Ditlevsen J, Hoch M, Emerich U, Axel D, Fingerle J, Meierkord S, Apfel H, Krippeit-Drews P, and Heinle H. Ca2+ entry and vasoconstriction during osmotic swelling of vascular smooth muscle cells. Pflügers Arch 431: 253258, 1995.[ISI][Medline]
20. Langton PD. Calcium channel currents recorded from isolated myocytes of rat basilar artery are stretch sensitive. J Physiol 471: 111, 1993.[Abstract]
21. Maertens C, Wei L, Droogmans G, and Nilius B. Inhibition of volume-regulated and calcium-activated chloride channels by the antimalarial mefloquine. J Pharmacol Exp Ther 295: 2936, 2000.
22. Matsuda N, Hagiwara N, Shoda M, Kasanuki H, and Hosoda S. Enhancement of the L-type Ca2+ current by mechanical stimulation in single rabbit cardiac myocytes. Circ Res 78: 650659, 1996.
23. McCarron JG, Crichton CA, Langton PD, MacKenzie A, and Smith GL. Myogenic contraction by modulation of voltage-dependent calcium currents in isolated rat cerebral arteries. J Physiol 498: 371379, 1997.[Abstract]
24. Mochly-Rosen D and Gordon AS. Anchoring proteins for protein kinase C: a means for isozyme selectivity. FASEB J 12: 3542, 1998.
25. Moran J, Sabanero M, Meza I, and Pasantes-Morales H. Changes of actin cytoskeleton during swelling and regulatory volume decrease in cultured astrocytes. Am J Physiol Cell Physiol 271: C1901C1907, 1996.
26. Ohya Y, Adachi N, Nakamura Y, Setoguchi M, Abe I, and Fujishima M. Stretch-activated channels in arterial smooth muscle of genetic hypertensive rats. Hypertension 31: 254258, 1998.
27. Oka N, Yamamoto M, Schwencke C, Kawabe J, Ebina T, Ohno S, Couet J, Lisanti MP, and Ishikawa Y. Caveolin interaction with protein kinase C. Isoenzyme-dependent regulation of kinase activity by the caveolin scaffolding domain peptide. J Biol Chem 272: 3341633421, 1997.
28. Okada Y. A scaffolding for regulation of volume-sensitive Cl channels. J Physiol 520: 2, 1999.
29. Prekeris R, Hernandez RM, Mayhew MW, White MK, and Terrian DM. Molecular analysis of the interactions between protein kinase C- and filamentous actin. J Biol Chem 273: 2679026798, 1998.
30. Prekeris R, Mayhew MW, Cooper JB, and Terrian DM. Identification and localization of an actin-binding motif that is unique to the isoform of protein kinase C and participates in the regulation of synaptic function. J Cell Biol 132: 7790, 1996.[Abstract]
31. Roman RM, Bodily KO, Wang Y, Raymond JR, and Fitz JG. Activation of protein kinase C couples cell volume to membrane Cl permeability in HTC hepatoma and Mz-ChA-1 cholangiocarcinoma cells. Hepatology 28: 10731080, 1998.[ISI][Medline]
32. Rybin VO, Xu X, and Steinberg SF. Activated protein kinase C isoforms target to cardiomyocyte caveolae: stimulation of local protein phosphorylation. Circ Res 84: 980988, 1999.
33. Sasaki N, Mitsuiye T, and Noma A. Effects of mechanical stretch on membrane currents of single ventricular myocytes of guinea-pig heart. Jpn J Physiol 42: 957970, 1992.[ISI][Medline]
34. Shimizu T, Morishima S, and Okada Y. Ca2+-sensing receptor-mediated regulation of volume-sensitive Cl channels in human epithelial cells. J Physiol 528: 457472, 2000.
35. Tsuzuki T, Okabe K, Kajiya H, and Habu T. Osmotic membrane stretch increases cytosolic Ca2+ and inhibits bone resorption activity in rat osteoclasts. Jpn J Physiol 50: 6776, 2000.[ISI][Medline]
36. Viard P, Macrez N, Mironneau C, and Mironneau J. Involvement of both G protein s and
subunits in
-adrenergic stimulation of vascular L-type Ca2+ channels. Br J Pharmacol 132: 669676, 2001.
37. Welsh DG, Nelson MT, Eckman DM, and Brayden JE. Swelling-activated cation channels mediate depolarization of rat cerebrovascular smooth muscle by hyposmolarity and intravascular pressure. J Physiol 527: 139148, 2000.
38. Yamamoto Y and Suzuki H. Two types of stretch-activated channel activities in guinea-pig gastric smooth muscle cells. Jpn J Physiol 46: 337345, 1996.[ISI][Medline]
39. Yamazaki J, Duan D, Janiak R, Kuenzli K, Horowitz B, and Hume JR. Functional and molecular expression of volume-regulated chloride channels in canine vascular smooth muscle cells. J Physiol 507: 729736, 1998.
40. Zhong J, Dessauer CW, Keef KD, and Hume JR. Regulation of L-type Ca2+ channels in rabbit portal vein by G protein s and
subunits. J Physiol 517: 109120, 1999.
41. Zhong J, Hume JR, and Keef KD. -Adrenergic receptor stimulation of L-type Ca2+ channels in rabbit portal vein myocytes involves both
s and
G protein subunits. J Physiol 531: 105115, 2001.
42. Zhong J, Wang GX, Hatton WJ, Yamboliev IA, Walsh MP, and Hume JR. Regulation of volume-sensitive outwardly rectifying anion channels in pulmonary arterial smooth muscle cells by protein kinase C. Am J Physiol Cell Physiol 283: C1627C1636, 2002.
|
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Visit Other APS Journals Online |