Circulation Research, Vol 71, 201-209, Copyright © 1992 by American Heart Association

ARTICLES

Effects of external pH on ionic currents in smooth muscle cells from the basilar artery of the guinea pig

GA West, DC Leppla and JM Simard
Department of Neurological Surgery, Unversity of Washington, Seattle.

pHo is an important determinant of vascular tone in cerebral blood vessels. We investigated the effects of changes in pHo on isolated smooth muscle cells from the basilar artery of the guinea pig. Single cells contracted rapidly in response to an elevation in pHo (constant CO2), and contraction was blocked by nifedipine, suggesting a role for dihydropyridine-sensitive Ca2+ channels. In whole-cell patch-clamp experiments, changes in pHo (pHo 5.7-8.1, pHi 7.2 with 10 mM HEPES) strongly affected the amplitude of the peak Ca2+ channel current (10 mM Ba2+, +15 mV, holding potential of -55 mV), with an apparent pK of 6.9. The current-voltage curves were minimally shifted, indicating no important effect of surface charge. To separate the slowly inactivating L-type Ca2+ channel current from the more rapidly inactivating B-type current, the decaying portions of inward currents from cells studied with repetitive 1-second pulses (+15 mV, holding potential of -55 mV) were fit to a two-component model. Titration curves for the L-type and B-type currents indicated maximum increases by factors of 3.65 and 1.28 at alkaline pHo and gave apparent pK values of 7.71 and 6.47 (Hill coefficient unity). The time constant of inactivation for the B-type current at +15 mV was little affected by pHo, whereas that for the L- type current increased somewhat with increasing pHo. Additional experiments showed no significant effect of pHo on holding current or on voltage-activated outward currents (pCai 7 with 11 mM EGTA). Our results provide additional evidence for participation of Ca2+ channels in regulating basal tone in cerebral smooth muscle and indicate that pHo regulates current through slowly inactivating, dihydropyridine- sensitive L-type Ca2+ channels.

This article has been cited by other articles:

				G. W. Britz, J. R. Meno, I.-S. Park, T. J. Abel, A. Chowdhary, T.-S. K. Nguyen, H. R. Winn, and A. C. Ngai Time-Dependent Alterations in Functional and Pharmacological Arteriolar Reactivity After Subarachnoid Hemorrhage Stroke, April 1, 2007; 38(4): 1329 - 1335. [Abstract] [Full Text] [PDF]

				T. J. Heppner, A. D. Bonev, L. F. Santana, and M. T. Nelson Alkaline pH shifts Ca2+ sparks to Ca2+ waves in smooth muscle cells of pressurized cerebral arteries Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2169 - H2176. [Abstract] [Full Text] [PDF]

				R. Springett, J. Newman, M. Cope, and D. T. Delpy Oxygen dependency and precision of cytochrome oxidase signal from full spectral NIRS of the piglet brain Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2202 - H2209. [Abstract] [Full Text] [PDF]

				V. Nazarov, J. Aquino-DeJesus, M. Apkon, and H. H. Dietrich Extracellular pH, Ca2+ Influx, and Response of Vascular Smooth Muscle Cells to 5-Hydroxytryptamine Editorial Comment Stroke, October 1, 2000; 31(10): 2500 - 2507. [Abstract] [Full Text] [PDF]

				S. V. Smirnov, G. A. Knock, A. E. Belevych, and P. I. Aaronson Mechanism of effect of extracellular pH on L-type Ca2+ channel currents in human mesenteric arterial cells Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H76 - H85. [Abstract] [Full Text] [PDF]

				C. Austin and S. Wray Interactions Between Ca2+ and H+ and Functional Consequences in Vascular Smooth Muscle Circ. Res., February 18, 2000; 86(3): 355 - 363. [Abstract] [Full Text] [PDF]

				X. Li and J. M. Simard Multiple Connexins Form Gap Junction Channels in Rat Basilar Artery Smooth Muscle Cells Circ. Res., June 11, 1999; 84(11): 1277 - 1284. [Abstract] [Full Text] [PDF]

				J. B. Gordon, T. R. Halla, C. D. Fike, and J. A. Madden Mediators of alkalosis-induced relaxation in pulmonary arteries from normoxic and chronically hypoxic piglets Am J Physiol Lung Cell Mol Physiol, January 1, 1999; 276(1): L155 - L163. [Abstract] [Full Text] [PDF]

				J. M. Simard, X. Li, and K. Tewari Increase in Functional Ca2+ Channels in Cerebral Smooth Muscle With Renal Hypertension Circ. Res., June 29, 1998; 82(12): 1330 - 1337. [Abstract] [Full Text] [PDF]

				G.L. Smith, C. Austin, C. Crichton, and S. Wray A review of the actions and control of intracellular pH in vascular smooth muscle Cardiovasc Res, May 1, 1998; 38(2): 316 - 331. [Abstract] [Full Text] [PDF]

				H.-L. Peng, P. E. Jensen, H. Nilsson, and C. Aalkjar Effect of acidosis on tension and [Ca2+]i in rat cerebral arteries: is there a role for membrane potential? Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H655 - H662. [Abstract] [Full Text] [PDF]

				C. J. Leech and J. E. Faber Differential Sensitivity of Venular and Arteriolar {alpha}-Adrenergic Receptor Constriction to Inhibition by Hypoxia : Role of Receptor Subtype and Coupling Heterogeneity Circ. Res., June 1, 1996; 78(6): 1064 - 1074. [Abstract] [Full Text]

				R. Tian, P. Vogel, N. A. Lassen, M. J. Mulvany, F. Andreasen, and C. Aalkjær Role of Extracellular and Intracellular Acidosis for Hypercapnia-Induced Inhibition of Tension of Isolated Rat Cerebral Arteries Circ. Res., February 1, 1995; 76(2): 269 - 275. [Abstract] [Full Text]