Inward current oscillation underlying tonic contraction caused via ET[sub A] receptors in pig detrusor smooth muscle.

Endothelin-I (ET-1) is a powerful vasoconstricting peptide. Recent studies showed synthesis of ET-1 and the presence of ET receptors in urinary bladder smooth muscle cells. In the present study, we investigated the possible role of ET-1 in detrusor contraction and its underlying mechanisms in terms of electrical activity. ET-1 caused dose-dependent tonic contraction of bladder smooth muscle strips. Whole cell patch-clamp experiments revealed that ET-1 induced a single transient inward current in the majority of detrusor cells and that additional inward current oscillations were induced in one-third of the cells. The inward current oscillation and tonic contraction shared several characteristic features: 1) both activities lasted for a considerable time after ET-1 washout and 2) only prior application of ET[sub A] receptor antagonists, not ET[sub B] receptor antagonists, significantly suppressed ET-1-induced contractions and the oscillating inward currents. It was concluded that the inward current oscillation underlies ET-1-induced tonic contraction. Experiments with ion substitution and channel blockers suggested that periodic activation of Ca[sup 2+]-activated Cl[sup -] channels caused the oscillating inward currents. [ABSTRACT FROM AUTHOR]