Electrophysiological effects of endothelin‐1 and their relationship to contraction in rat renal arterial smooth muscle

The electophysiological effects of endothelin‐1 (ET‐1) and their relationship to contraction remain unclear in the renal circulation. Using endotheliumdenuded arteries from the main branch of the renal artery proximal to the kidney of the rat, we have examined its effects on tension and conducted parallel patch‐clamp measurements using freshly isolated smooth muscle cells from this tissue. Pharmacological experiments revealed that ET‐1 produced constriction of renal arteries dependent on the influx of extracellular Ca2+, mediated solely through ETA receptor stimulation. Current‐clamp experiments revealed that renal arterial myocytes had a resting membrane potential of ∼32 mV, with the majority of cells exhibiting spontaneous transient hyperpolarizations (STHPs). Application of ET‐1 produced depolarization and in those cells exhibiting STHPs, either caused their inhibition or made them occur regularly. Under voltage‐clamp conditions cells were observed to exhibit spontaneous transient outward currents (STOCs) inhibited by iberiotoxin. Application of voltage‐ramps revealed an outward current activated at ∼−30 mV, sensitive to both 4‐AP and TEA. Taken together these results suggest that renal arterial myocytes possess both delayed rectifying K+ (KV) and Ca2+‐activated K+ (BKCa) channels. Under voltage‐clamp, ET‐1 attenuated the outward current and reduced the magnitude and incidence of STOCs: effects mediated solely as a consequence of ETA receptor stimulation. Thus, in conclusion, activation of ETA receptors by ET‐1 causes inhibition of KV and BKCa channel activity, which could promote and/or maintain membrane depolarization. This effect is likely to favour L‐type Ca2+ channel activity providing an influx pathway for extracellular Ca2+ essential for contraction. British Journal of Pharmacology (2000) 130, 787–796; doi:10.1038/sj.bjp.0703377