The sodium-calcium exchanger is a mechanosensitive transporter

This report describes the influence of fluid flow and osmotically induced volume changes on Na⁺-Ca² exchange (NCX) activity in transfected CHO cells. Exchange activity was measured as Na⁺-dependent Ca² or Ba² fluxes using the fluorescent probe fura-2. When exchange activity was initiated by superfusing Ba²⁺-containing solutions over the cells for a 20 s interval, a high rate of Ba²⁺ uptake was observed while the solution was being applied but the rate of Ba²⁺ uptake declined > 10-fold when the solution flow ceased. Ba²⁺ efflux in exchange for extracellular Na⁺ or Ca²⁺ (Ba²⁺-Ca²⁺ exchange) was similarly biphasic. During NCX-mediated Ca²⁺ uptake, a rapid increase in cytosolic [Ca²⁺ ]to a peak value occurred, followed by a decline in [Ca²⁺] i to a lower steady-state value after solution flow ceased. When NCX activity was initiated by an alternate procedure that minimized the duration of solution flow, the rapid phase of Ba²⁺ influx was greatly reduced in magnitude and Ca²⁺ uptake became nearly monophasic. Solution superfusion did not produce any obvious changes in cell shape or volume. NCX-mediated Ba²⁺ and Ca²⁺ influx were also sensitive to osmotically induced changes in cell volume. NCX activity was stimulated in hypotonic media and inhibited in hypertonic media; the osmotically induced changes in activity occurred within seconds and were rapidly reversible. We conclude that NCX activity is modulated by both solution flow and osmotically induced volume changes.