REGULATION OF CALCIUM-ACTIVATED POTASSIUM CHANNELS BY S-NITROSOTHIOL COMPOUNDS AND CYCLIC GUANOSINE-MONOPHOSPHATE IN RABBIT CORONARY-ARTERYMYOCYTES

Background: The patch-clamp technique was used to study a large conduc tance, calcium-activated potassium channel (I-K(Ca)) in coronary arter ial smooth muscle cells from rabbits, The properties of this channel a re similar to those of I-K(Ca) found in many types of vascular tissue. A brief single channel characterization of I-K(Ca) in this tissue typ e has been completed for this study. Methods: The effects of S-nitroso thiol compounds on I-K(Ca) were studied in cell-attached patches. Resu lts: The probability of opening for I-K(Ca) increased from 0.008 +/- 0 .001 to 0.780 +/- 0.07 following application of S-nitroso-1 cysteine. S-nitroso-N-acetylpenicillamine (SNAP) also increased the probability of opening for I-K(Ca) from 0.022 +/- 0.01 to 0.601 +/- 0.05. The prob ability of opening for I-K(Ca) also increased from 0.026 +/- 0.01 to 0 .809 +/- 0.02 following application of membrane-permeable analogs of c yclic guanosine monophosphate (cGMP) to the bath of cell-attached patc hes, suggesting that I-K(Ca) in coronary artery smooth muscle cells is regulated by a cGMP-dependent mechanism, Rp-8-pCPT-cGMP, a protein ki nase G inhibitor, blocked the effect of SNAP, an S-nitrosothiol compou nd. Conclusions: These findings suggest that one of the effects of nit rosothiol compounds is the activation of I-K(Ca) through a cGMP-depend ent mechanism in coronary artery smooth muscle cells.