Nitric oxide activates Ca2+-activated K+ channels in cultured bovine adrenal chromaffin cells

The effects of sodium nitroprusside (SNP) on Ca2+-dependent Kf (KCa) channels in cultured bovine adrenal chromaffin cells were investigated using single channel recording patch-clamp techniques. KCa channels were activated by application of 100 mu M SNP to the extracellular side of cell-attached patches. Methylene blue (300 mu M), an inhibitor of soluble guanylate cyclase, or H-8 (1 mu M), a protein kinase inhibitor with relative specificity for cGMP-dependent protein kinase, diminished but did not completely abolish the SNP-induced KCa channel activation. Diethylamine/NO complex (DEA/NO), an NO donor, also activated KCa channels in cell-attached patches. Furthermore, application of 100 mu M SNP or 100 nM DEA/NO to the intracellular surface of excised inside-out patches also activated KCa channels in the bath solution which contained 1 mu M Ca2+. These results indicate that SNP is capable of activating the KCa channel via cGMP-dependent and -independent mechanisms. These studies demonstrate that NO may serve as an important regulatory mechanism for catecholamine secretion in chromaffin cells via the activation of KCa channels. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.