Characterisation of the ionic currents in freshly isolated rat ureter smooth muscle cells: evidence for species-dependent currents.

Abstract

To better understand excitability, and hence contraction, the ionic currents underlying the action potential were identified and characterised in enzymatically isolated smooth muscle cells of the rat ureter. Using the whole-cell patch-clamp, under voltage-clamp conditions with K(+) in the pipette, three types of responses occurred to depolarisation: (1) sustained outward current and spontaneous transient outward currents (STOCs); (2) inward current; and (3) fast outward current. Investigation using different voltage protocols and pharmacological blockers and agonists revealed the presence of three outward and two inward currents. The outward currents were: (1) a sustained BK current, sensitive to low concentrations of tetraethylammonium (TEA) and featuring bursts of STOCs superimposed on it; (2) a fast, transient, A-type K current sensitive to 4-aminopyridine; and (3) a TEA and Ca(2+)-insensitive, late K(+) rectifier current. The inward currents were: (1) a fast L-type Ca(2+) channel current sensitive to nifedipine, Cd(2+) and potentiated by Ba(2+); and (2) a Ca(2+)-sensitive Cl(-) channel, which was inhibited by niflumic acid and Ba(2+), and produced a large tail current upon repolarisation at the end of the voltage step. The I- V relationships and peak amplitudes of all the currents are described. The finding of a K(+) rectifier and Ca(2+)-activated Cl(-) channel distinguish the rat ureteric cells from those of the guinea-pig. Thus, as well as the previously established difference in sarcoplasmic reticulum Ca(2+)-release mechanisms, there is also a species difference in ion channel expression in this tissue. We relate these currents to their possible contribution to the characteristically extremely long lasting action potential in the rat ureter.