Sodium nitroprusside and cGMP decrease Ca2+ channel availability in basilar artery smooth muscle cells.
We studied the effect of the nitric oxide (NO) donor, sodium nitroprusside (SNP), on the macroscopic and single-channel currents due to the 22-pS Ca2+ channel in smooth muscle cells from guinea pig basilar artery. In nystatin-perforated whole-cell recordings, 50 nM SNP decreased the macroscopic current to 63+/-12% of control values, without changing the voltage dependence of the current. In cell-attached patches with BAY-K8644 in the pipette, SNP caused a comparable decrease in single-channel availability (n . Po) that was dose dependent over the range of 10 nM to 10 microM SNP. SNP had no effect on single-channel properties, including slope conductance, voltage dependence of activation, the number of open states, the time constants of the open states, and the proportion of time spent in each open state. The effect of SNP (50 nM) on single Ca2+ channel openings was reproduced by 8-Br-cGMP (100 microM), which also reduced channel availability without altering channel properties. The protein kinase inhibitor H-8 (1.5 microM), which exhibits relative specificity for cGMP-dependent protein kinase, completely inhibited the decrease in single-channel availability expected with SNP. The dose-dependent decrease in Ca2+ channel availability caused by SNP was not altered by prior application of 8-Br-cAMP or forskolin, both of which cause an increase in Ca2+ channel availability in these cells. Our findings suggest that NO decreases openings of Ca2+ channels in basilar artery smooth muscle cells without altering channel properties, and that it does so by a mechanism likely to involve cGMP-dependent protein kinase.
Tewari
K
K
University of Maryland School of Medicine, Baltimore MD 21201, USA.
Simard
J M
JM
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D015220:Calcium Channels / Q000187:drug effects*; D006152:Cyclic GMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D009130:Muscle, Smooth / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*
D015220:Calcium Channels; D009599:Nitroprusside; D006152:Cyclic GMP