Temporal changes in atrial EC-coupling during prolonged stimulation with endothelin-1

Bootman, Martin D.; Harzheim, Dagmar; Smyrnias, Ioannis; Conway, Stuart J. and Roderick, H. Llewelyn (2007). Temporal changes in atrial EC-coupling during prolonged stimulation with endothelin-1. Cell calcium, 42(4-5) pp. 489–501.

DOI: https://doi.org/10.1016/j.ceca.2007.05.004

Abstract

Endothelin-1 (ET-1) is a potent G_q-coupled agonist with important physiological effects on the heart. In the present study, we characterised the effect of prolonged ET-1 stimulation on Ca²⁺ signalling within acutely isolated atrial myocytes. ET-1 induced a reproducible and complex sequence of effects, including negative inotropy, positive inotropy and pro-arrhythmic spontaneous Ca²⁺transients (SCTs). The negative and positive inotropic effects correlated with the ability of Ca²⁺to propagate from the subsarcolemmal sites where EC-coupling initiates into the centre of the atrial cells. We examined the spatial and temporal properties of the SCTs and observed them to range from elementary Ca²⁺sparks, flurries of Ca²⁺sparks, to Ca²⁺waves and action potential-evoked global Ca²⁺transients. The positive inotropic effect of ET-1 and its ability to trigger SCTs were mimicked by direct stimulation of InsP₃Rs. An antagonist of InsP₃Rs prevented the generation of SCTs and partially reduced the positive inotropy evoked by ET-1. Our data suggest that ET-1 engages multiple signal transduction pathways to provoke a plethora of different responses within an atrial myocyte. Some of the actions of ET-1 appear to be due to stimulation of InsP₃Rs.

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