Patterns of excitation-contraction coupling in arterioles: dependence on time and concentration

Abstract

We sought to understand the excitation-contraction coupling process in arterioles. KCl or phenylephrine (PE) was applied via the superfusion solution or by brief pulsatile ejections from a micropipette onto unpressurized arterioles (in vitro) from either the guinea pig small intestine or hamster cheek pouch. With either mode of application, KCl caused depolarizations that were tightly and predictably correlated with subsequent constrictions (electromechanical coupling). In contrast, the relationship between membrane potential and vasoconstriction in response to phenylephrine was dependent on both stimulus duration and agonist concentration. Application of short pulses of PE (<1 s) produced mechanical responses that were dominated by pharmacomechanical coupling (i.e., they were not associated with changes in membrane potential). With longer PE stimuli, electromechanical coupling became more important and dominated microvessel responses. We conclude that adequate understanding of the signaling process in microvessels requires a consideration of both concentration and duration of application. Both the mode and duration of agonist application affect the relative degree of electromechanical or pharmacomechanical coupling in response to a vasomotor stimulus. These observations have important implications for intracellular and intercellular signaling.