Intracellular Ca2+ Silences L-Type Ca2+ Channels in Mesenteric Veins

Rationale: Calcium channel blockers (CCBs) exert their antihypertensive effect by reducing cardiac afterload but not preload, suggesting that Ca2+ influx through L-type Ca2+ channels (LTCC) mediates arterial but not venous tone. Objective: The object of this study was to resolve the mechanism of venous resistance to CCBs. Methods and Results: We compared the sensitivity of depolarization (KCl)-induced constriction of rat small mesenteric arteries (MAs) and veins (MVs) to the dilator effect of CCBs. Initial findings confirmed that nifedipine progressively dilated depolarization-induced constrictions in MAs but not MVs. However, Western blots showed a similar expression of the α1C pore-forming subunit of the LTCC in both vessels. Patch-clamp studies revealed a similar density of whole-cell Ca2+ channel current between single smooth muscle cells (SMCs) of MAs and MVs. Based on these findings, we hypothesized that LTCCs are expressed but “silenced” by intracellular Ca2+ in venous SMCs. After depletion of intr...