Regulation of calcium-activated potassium channels by S-nitrosothiol compounds and cyclic guanosine monophosphate in rabbit coronary artery myocytes.

BACKGROUND

The patch-clamp technique was used to study a large conductance, calcium-activated potassium channel (IK(Ca) in coronary arterial smooth muscle cells from rabbits. The properties of this channel are similar to those of IK(Ca) found in many types of vascular tissue. A brief single channel characterization of IK(Ca) in this tissue type has been completed for this study.

METHODS

The effects of S-nitrosothiol compounds on IK(Ca) were studied in cell-attached patches.

RESULTS

The probability of opening for IK(Ca) increased from 0.008 +/- 0.004 to 0.780 +/- 0.07 following application of S-nitroso-L-cysteine. S-nitroso-N-acetylpenicillamine (SNAP) also increased the probability of opening for IK(Ca) from 0.022 +/- 0.01 to 0.601 +/- 0.05. The probability of opening for IK(Ca) also increased from 0.026 +/- 0.01 to 0.809 +/- 0.02 following application of membrane-permeable analogs of cyclic guanosine monophosphate (cGMP) to the bath of cell-attached patches, suggesting that IK(Ca) in coronary artery smooth muscle cells is regulated by a cGMP-dependent mechanism. Rp-8-pCPT-cGMP, a protein kinase G inhibitor, blocked the effect of SNAP, an S-nitrosothiol compound.

CONCLUSIONS

These findings suggest that one of the effects of nitrosothiol compounds is the activation of IK(Ca) through a cGMP-dependent mechanism in coronary artery smooth muscle cells.