[Na.sup.+] entry via store-operated channels modulates [Ca.sup.2+] signaling in arterial myocytes

Arnon, Assaf, John M. Hamlyn, and Mordecai P. Blaustein. [Na.sup.+] entry via store-operated channels modulates [Ca.sup.2+] signaling in arterial myocytes. Am J. Physiol. Cell Physiol. 278: C163-C173, 2000.--In many nonexcitable cells, hormones and neutransmitters activate [Na.sup.+] influx and mobilize [Ca.sup.2+] from intracellular stores. The stores are replenished by [Ca.sup.2+] influx via 'store-operated' [Ca.sup.2+] channels (SOC). The main routes of [Na.sup.+] entry in these cells are unresolved, and no role for [Na.sup.+] in signaling has been recognized. We demonstrate that the SOC are a major [Na.sup.+] entry route in arterial myocytes. Unloading of the [Ca.sup.2+] stores with cyclopiazonic acid (a sarcoplasmic reticulum [Ca.sup.2+] pump inhibitor) and caffeine induces a large external [Na.sup.+]-dependent rise in the cytosolic [Na.sup.+] concentration. One component of this rise in cytosolic [Na.sup.+] concentration is likely due to [Na.sup.+]/[Ca.sup.2+] exchange; it depends on elevation of cytosolic [Ca.sup.2+] and is insensitive to 10 mM [Mg.sup.2+] and 10 [micro]M [La.sup.3+]. Another component is inhibited by [Mg.sup.2+] and [La.sup.3+], blockers of SOC; this component persists in cells preloaded with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid to buffer [Ca.sup.2+] transients and prevent [Na.sup.+]/[Ca.sup.2+] exchange-mediated [Na.sup.+] entry. This [Na.sup.+] entry apparently is mediated by SOC. The [Na.sup.+] entry influences [Na.sup.+] pump activity and [Na.sup.+]/ [Ca.sup.2+] exchange and has unexpectedly large effects on cell-wide [Ca.sup.2+] signaling. The SOC pathway may be a general mechanism by which [Na.sup.+] participates in signaling in many types of cells. sodium-calcium exchange; magnesium; sodium pump; cytosolic sodium concentration