Cross Talk Between Plasma Membrane Na+/Ca2+ Exchanger-1 and TRPC/Orai-Containing Channels: Key Players in Arterial Hypertension

Arterial smooth muscle (ASM) Na(+)/Ca(2+) exchanger type 1 (NCX1) and TRPC/Orai-containing receptor/store-operated cation channels (ROC/SOC) are clustered with α2 Na(+) pumps in plasma membrane microdomains adjacent to the underlying junctional sarcoplasmic reticulum. This arrangement enables these transport proteins to function as integrated units to help regulate local Na(+) metabolism, Ca(2+) signaling and arterial tone. They thus influence vascular resistance and blood pressure (BP). For instance, up-regulation of NCX1 and TRPC6 has been implicated in the pathogenesis of high BP in several models of essential hypertension: ouabain-induced hypertensive rats, Milan hypertensive strain rats, and Dahl salt-sensitive hypertensive rats, which all have elevated plasma ouabain levels. Enhanced expression and function of arterial smooth muscle NCX1 and TRPC/Orai1-containing channels in experimental and clinical hypertension implies that these proteins are potential targets for pharmacological intervention