Endothelin enhances activity of mechanosensitive channels: A mechanism for ET augmentation of the myogenic response

Abstract

See article by Lee et al. [11] (pages 224–235) in this issue. That stretching smooth muscle can result in contraction has been appreciated for over a hundred years (see [1]), and Bayliss in 1902 [1] demonstrated that an increase in luminal pressure in arteries resulted in passive distension followed by constriction. Neural and hormonal mechanisms were excluded, so mechanisms intrinsic to smooth muscle were invoked to explain this phenomenon, now known as the myogenic response. Reports of stretch-induced activation of depolarization[2] and action potentials [3] in visceral smooth muscle were followed by studies on blood vessels in which increases in luminal pressure were associated with depolarization [4–6] and the initiation of action potentials [4]. Attenuation of the myogenic constriction by Ca2+channel blockers implicated voltage-operated Ca2+channels. But what causes the critical depolarization that activates the Ca2+channels? In a wide range of cell types, including vascular smooth muscle [7], negative pressure applied to patch-clamp electrodes activates various ion channels, particularly poorly selective cation channels. Thus, pressurization of blood vessels stretches their walls which activates stretch-sensitive cation channels, resulting in depolarization that activates voltage-operated Ca2+ channels, and the ensuing influx of Ca2+ initiates constriction. However, additional dimensions add complexity and raise further questions. These are generally centred on the processes that underlie stretch activation of ion channels, the role of the … *Corresponding author. Tel.: +61 3 9905 2520; fax: +61 3 9905 2547. h.coleman{at}med.monash.edu.au