Phenylephrine contracts rat tail artery by one electromechanical and three pharmacomechanical mechanisms
Chen, X.L.; Rembold, C.M.
American Journal of Physiology 268(1 Pt 2): H74-H81
1995
ISSN/ISBN: 0002-9513 PMID: 7840305 Document Number: 442683
There are at least four mechanisms hypothesized to account for excitation-contraction coupling in arterial smooth muscle. 1) Contractile agonists and changes in extracellular (K+) ((K+)-o) induce contraction by depolarization, which increases Ca-2+ influx; this is the only mechanism involving a change in membrane potential (E-m). 2) Contractile agonists release Ca-2+ from the intracellular Ca-2+ store. 3) Contractile agonists increase Ca-2+ influx without changing E-m either by activating voltage-dependent L-type Ca-2+ channels or by opening other Ca-2+-permeable channels. 4) Contractile agonists increase intracellular Ca-2+ ((Ca-2+)-i) sensitivity of force; this is the only mechanism that does not involve changes in (Ca-2+)-i. Each of these mechanisms has been demonstrated in intact, skinned, or dissociated smooth muscle preparations. However, these four mechanisms have not been compared in the same preparation. The goal of this study was to determine which of these four contractile mechanisms are physiologically relevant in the intact rat tail artery. We stimulated deendothelialized rat tail artery with phenylephrine and high (K+)-o. We then measured E-m with microelectrodes, (Ca-2+)-i with fura 2, and isometric force with a strain gauge transducer. We find that all four mechanisms contributed to phenylephrine-induced rat tail artery contraction. The majority of phenylephrine-induced contraction was caused by depolarization and by increases in the (Ca-2+)-i sensitivity of force. Low concentrations of phenylephrine also increased (Ca-2+) independent of changes in E-m, potentially by increases in Ca-2+ influx. Release of Ca-2+ from intracellular stores was only observed with high concentrations of phenylephrine. Smooth muscle appears to invoke multiple mechanisms for excitation-contraction coupling.