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 relationship to contraction remain unclear in the renal circulation. Using endothelium-denuded 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. 2 Pharmacological experiments revealed that ET-1 produced constriction of renal arteries dependent on the influx of extracellular Ca2+, mediated solely through ETA receptor stimulation. 3 Current-clamp experiments revealed that renal arterial myocytes had a resting membrane potential of similar to 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. 4 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 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+-activated 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 inhibition of K-V 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.