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

1 The electophysiological effects of endothelin-1 (ET-1) and their relation ship to contraction remain unclear in the renal circulation. Using endothel ium-denuded arteries from the main branch of the renal artery proximal to t he kidney of the rat, we have examined its effects on tension and conducted parallel patch-clamp measurements using freshly isolated smooth muscle cel ls from this tissue. 2 Pharmacological experiments revealed that ET-1 produced constriction of r enal arteries dependent on the influx of extracellular Ca2+, mediated solel y through ETA receptor stimulation. 3 Current-clamp experiments revealed that renal arterial myocytes had a res ting membrane potential of similar to 32 mV, with the majority of cells exh ibiting spontaneous transient hyperpolarizations (STHPs). Application of ET -1 produced depolarization and in those cells exhibiting STHPs, either caus ed their inhibition or made them occur regularly. 4 Under voltage-clamp conditions cells were observed to exhibit spontaneous transient outward currents (STOCs) inhibited by iberiotoxin. Application o f voltage-ramps revealed an outward current activated at similar to -30 mV, sensitive to both 4-AP and TEA. Taken together these results suggest that renal arterial myocytes possess both delayed rectifying K+ (K-V) and Ca2+-a ctivated K+ (BKCa,) channels. 5 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. 6 Thus, in conclusion, activation of ETA receptors by ET-1 causes inhibitio n of K-V and BKCa channel activity, which could promote and/or maintain mem brane depolarization. This effect is likely to favour L-type Ca2+ channel a ctivity providing an influx pathway for extracellular Ca2+ essential for co ntraction.