Hypoxia inhibits the Na(+)/Ca(2+) exchanger in pulmonary artery smooth muscle cells

The cellular mechanisms underlying hypoxic pulmonary vasoconstriction are not fully understood. We examined the effect of hypoxia on Ca(2+) efflux from the cytosol in single Fura-2-loaded pulmonary artery myocytes. During mild hypoxia (pO(2)=50-60 Torr), peak [Ca(2+)](i) was increased and the rate of Ca(2+) removal from the cytosol was markedly slowed after stimuli that elevated [Ca(2+)](i). Removal of extracellular Na(+) potentiated the peak [Ca(2+)](i) rise and slowed the Ca(2+) decay rate in cells recorded under normoxic conditions; it did not further slow the Ca(2+) decay rate or potentiate the [Ca(2+)](i) increase in hypoxic cells. An Na(+)/Ca(2+) exchange current was recorded in isolated pulmonary artery myocytes. Switching from Li(+) to Na(+) (130 mM) revealed an inward current with reversal potential consistent with the Na(+)/Ca(2+) exchange current in cells in which [Ca(2+)](i) was clamped at 1 microM similar currents, although smaller, were observed with normal resting [Ca(2+)](i) using the perforated patch clamp technique. The Na(+)/Ca(2+) exchange current was markedly inhibited in myocytes exposed to mild hypoxia. RT-PCR revealed the expression of specific alternatively spliced RNAs of NCX1 in rat pulmonary arteries. These findings provide an enhanced understanding of the molecular mechanisms underlying hypoxic sensing in pulmonary arteries.