Distinct roles for L- and T-type Ca²⁺channels in regulation of atrial ANP release

Abstract

Atrial secretion of atrial natriuretic peptide (ANP) has been shown to be regulated by atrial workload. Although modulating factors for the secretion of ANP have been reported, the role for intracellular Ca(2+) on the secretion of ANP has been controversial. The purpose of the present study was to define roles for L- and T-type Ca(2+) channels in the regulation of ANP secretion in perfused beating rabbit atria. BAY K 8644 (BAY K) increased atrial stroke volume and pulse pressure. BAY K suppressed ANP secretion and ANP concentration in terms of extracellular fluid (ECF) translocation concomitantly with an increase in atrial dynamics. BAY K shifted the relationship between ANP secretion and ECF translocation downward and rightward. These results indicate that BAY K inhibits myocytic release of ANP. In the continuous presence of BAY K, diltiazem reversed the effects of BAY K. Diltiazem alone increased ANP secretion and ANP concentration along with a decrease in atrial dynamics. Diltiazem shifted relationships between ANP secretion and atrial stroke volume or ECF translocation leftward. The T-type Ca(2+) channel inhibitor mibefradil decreased atrial dynamics. Mibefradil inhibited ANP secretion and ANP concentration in contrast with the L-type Ca(2+) channel inhibitor. These results suggest that activation of L- and T-type Ca(2+) channels elicits opposite effects on atrial myocytic release of ANP.

Osmoregulation of atrial myocytic ANP release: osmotransduction via cross-talk between L-type Ca2+channel and SR Ca2+release

“…Similarly, sarcolemmal (SL) L-type Ca 2ϩ channel blocker inhibits ANP secretion in perfused hearts (38), isolated beating atria (39), and contracting atrial myocytes (30). In contrast, some reports, including ours, indicate that Ca 2ϩ is negatively involved in the regulation of ANP release in perfused hearts (20,37) and isolated beating atria (12,47).…”

“…L-type Ca 2ϩ channel blockade attenuated hyperosmolalityinduced increase in atrial myocytic ANP release. Previously, it was shown that L-type Ca 2ϩ channel activation with Bay K 8644 decreased and inhibition with inhibitors increased atrial ANP release in beating rabbit atria (47). This means that the Ca 2ϩ entry via L-type Ca 2ϩ channels inhibits atrial myocytic ANP release.…”

“…Ca 2ϩ entry via SL L-type Ca 2ϩ channel activation decreases atrial myocytic ANP release (22,47). It was shown that SR Ca 2ϩ release was positively (9,21,24,26,30,39) or negatively (29) channels in the regulation of atrial ANP release has yet to be defined.…”

Protein kinase-dependent and Ca2+-independent cAMP inhibition of ANP release in beating rabbit atria

“…In contrast, Ca 2ϩ has also been reported to be a negative regulator for ANP secretion in perfused heart (13,25) and isolated beat-ing (8,17,33) and nonbeating atria (4,9,14). Recently (33) it was shown that L-and T-type Ca 2ϩ channels are involved in the opposite regulation of myocytic ANP release.…”

“…This means that the mechanism by which staurosporine blocks the cAMP-induced inhibition of ANP release may be related to protein kinase(s) other than PKA, PKC-␣, and Ca 2ϩ /calmodulin kinase. Because the cAMP signaling pathway contains cAMP-related activation of L-type Ca 2ϩ channels (11,22) and also because an increase in the intracellular Ca 2ϩ concentration inhibits ANP release in beating atria and perfused heart (8,13,17,25,33) (33).…”