pH1 is an important determinant of vascular tone in cerebral blood vessels. We investigated the effects of changes in pH. on isolated smooth muscle cells from the basilar artery of the guinea pig. Single cells contracted rapidly in response to an elevation in pH. (constant C02), and contraction was blocked by nifedipine, suggesting a role for dihydropyridine-sensitive Ca2+ channels. In whole-cell patch-clamp experiments, changes in pH, (pH0 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 pH1 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 pH., whereas that for the L-type current increased somewhat with increasing pHo. Additional experiments showed no significant effect of pH, on holding current or on voltage-activated outward currents (pCaj 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 pH0 regulates current through slowly inactivating, dihydropyridine-sensitive L-type Ca2' channels. (Circulation Research 1992;71:201-209) KEY WoRDs * Ca2+ channels * K+ channels * pH * smooth muscle cells * basilar artery T he importance of acid-base balance in determining cerebral vascular tone has long been recognized. In 1849, Donders' observed in cranial window preparations that hypoventilation resulted in dilation of pial vessels, and in 1881, Mosso2 reported that hypoventilation caused a decrease in cerebrospinal fluid pulsations in patients with cranial defects. In the modern practice of neurosurgery, the relation between acid-base balance and cerebral blood flow remains axiomatic and is frequently exploited for therapeutic purposes. In patients with increased intracranial pressure, mechanical hyperventilation is used to induce respiratory alkalosis, resulting in cerebral vasoconstriction, a decrease in cerebral blood volume, and a decrease in intracranial pressure.An important question that gained early attention concerned the relative role of pHi versus pH,,I in medi-

No abstract

No abstract

No abstract