Using the patch-clamp recording technique, we observed that endothelin-1 (ET-1; 0.8-16 nM) enhanced a voltage-activated outward current (I(out)) and induced periodic oscillations of inward current in smooth muscle cells isolated from small pulmonary arteries (200-400 μm in diameter). Anion substitution experiments revealed that the ET-1-induced inward current was carried by Cl- ions. Application of bosentan (10 μM; an ET(A) and ET(B) receptor antagonist) and FR 139317 (1-10 μM; a selective ET(A) receptor antagonist) prevented initiation of inward currents or enhancement of I(out) by ET-1. The ET(B) receptor agonist tetra-Ala-endothelin-1 (1-20 nM) failed to evoke these responses. Caffeine (10 mM) induced a single transient inward current and prevented any further activation of inward current, or enhancement of I(out), by subsequent application of 16 nM ET-1, suggesting that these currents were mediated by Ca2+ release from internal stores. Rapid intracellular release of Ca2+ by photolysis of nitr-5 activated an inward Cl- current and increased the magnitude of I(out). These results demonstrate the existence of Ca2+ activated C- and K+ channels in pulmonary arterial smooth muscle. The physiological role of these channels is at present uncertain, although their activation may be involved in the contractile responses of pulmonary arterial smooth muscle to ET-1.
|Number of pages||10|
|Publication status||Published - 1995|
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