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.
Department of Physiology and Biophysics, University of Iowa, College of Medicine, Iowa City 52242, USA.
M J
MJ
George
E F
EF
Shibata
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism*; D006152:Cyclic GMP / Q000494:pharmacology*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D026403:S-Nitrosothiols; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D026423:S-Nitroso-N-Acetylpenicillamine; C021315:S-nitrosocysteine; D010396:Penicillamine; D006152:Cyclic GMP; D003545:Cysteine; D002118:Calcium