IONIC CURRENTS AND ENDOTHELIN SIGNALING IN SMOOTH-MUSCLE CELLS FROM RAT RENAL RESISTANCE ARTERIES

The repertoire of ionic channels expressed in myocytes freshly isolate d from microdissected interlobar and arcuate arteries of rat kidney an d their integrative behavior in response to endothelin-1 (ET-1) were s tudied by identification and characterization of major whole cell curr ent components using patch-clamp technique. In renal microvascular smo oth muscle cells (RMSMC) dialyzed with K+-containing solution, rapidly inactivating (I-to) and sustained outward K+ currents were identified . Voltage-dependent I-to was categorized as ''A'' current based on its kinetics, sensitivity to 4-aminopyridine (4-AP), and refractoriness t o tetraethylammonium (TEA(+)). Ca2+-activated component of K+ current was completely blocked by 10 mM TEA(+), whereas 5 mM 4-AP did not affe ct this current. Maximal Ca2+ current (I-Ca) recorded in Cs+-loaded RM SMC reached 250 pA when cells were bathed in a solution with 2.5 mM Ca 2+. Two patterns of I-Ca differing in kinetics, voltage range of activ ation and inactivation, and sensitivity to nifedipine were identified as T and L currents. Ca2+-dependent current component showing reversal potential near Cl- current (E(Cl)) and sensitivity to blocking action of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid was identified as Ca2+-activated E(Cl). Activation of RMSMC with ET-1 (1-10 nM) induced elevation of [Ca2+](i) and subsequent activation of Ca2+-activated I- Cl, which led to membrane depolarization sufficient to activate voltag e-gated Ca2+ channels. ET-1-evoked transient reduction of I-Ca carried through voltagegated Ca2+ channels was followed by augmentation of L- type I-Ca. ET-1-induced mobilization of intracellular Ca2+, accompa ni ed by membrane depolarization, resulted in activation of Ca2+-dependen t K+ channels, which can play the role of a feedback element terminati ng ET-1-induced membrane depolarization.