Acetylcholine‐induced membrane potential changes in endothelial cells of rabbit aortic valve

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Abstract
Using a microelectrode technique, acetylcholine (ACh)‐induced membrane potential changes were characterized using various types of inhibitors of K+ and Cl− channels in rabbit aortic valve endothelial cells (RAVEC). ACh produced transient then sustained membrane hyperpolarizations. Withdrawal of ACh evoked a transient depolarization. High K+ blocked and low K+ potentiated the two ACh‐induced hyperpolarizations. Charybdotoxin (ChTX) attenuated the ACh‐induced transient and sustained hyperpolarizations; apamin inhibited only the sustained hyperpolarization. In the combined presence of ChTX and apamin, ACh produced a depolarization. In Ca2+‐free solution or in the presence of Co2+ or Ni2+, ACh produced a transient hyperpolarization followed by a depolarization. In BAPTA‐AM‐treated cells, ACh produced only a depolarization. A low concentration of A23187 attenuated the ACh‐induced transient, but not the sustained, hyperpolarization. In the presence of cyclopiazonic acid, the hyperpolarization induced by ACh was maintained after ACh removal; this maintained hyperpolarization was blocked by Co2+. Both NPPB and hypertonic solution inhibited the membrane depolarization seen after ACh washout. Bumetanide also attenuated this depolarization. It is concluded that in RAVEC, ACh produces a two‐component hyperpolarization followed by a depolarization. It is suggested that ACh‐induced Ca2+ release from the storage sites causes a transient hyperpolarization due to activation of ChTX‐sensitive K+ channels and that ACh‐activated Ca2+ influx causes a sustained hyperpolarization by activating both ChTX‐ and apamin‐sensitive K+ channels. Both volume‐sensitive Cl− channels and the Na+‐K+‐Cl− cotransporter probably contribute to the ACh‐induced depolarization. British Journal of Pharmacology (1999) 126, 19–26; doi:10.1038/sj.bjp.0702262