Dual effect of external Ca2+ on noradrenaline-activated cation current in rabbit portal vein smooth muscle cells

1. The influence of divalent cations was investigated on the noradrenaline-activated nonselective cation current (I-cat) in freshly dispersed smooth muscle cells of rabbit portal vein. 2. Reduction of external calcium concentration ([Ca2+](o)) from 1.5 mM to 'test' levels of 100-500 mu M during stimulation of I-cat produced a sustained potentiation of I-cat, which indicates an inhibitory action of Ca-o(2+). With 'test' concentrations lower than 100 mu M Ca-o(2+) the amplitude of I-cat was initially potentiated and then the current subsequently declined. Under these conditions re-addition of 1.5 mM Ca-o(2+) transiently activated I-cat which demonstrates an additional facilitatory action of [Ca2+](o). The half-maximal [Ca2+](o) for the facilitatory and inhibitory action on I-cat was 6 and 400 mu M, respectively. 3. When [Ca2+](o) was decreased to very low levels (< 10 nM) by inclusion of 1 mM BAPTA in nominally Ca2+-free external solution, I-cat could still be evoked by noradrenaline. This suggested that Ca2+ is not obligatory for activation of I-cat but merely modulatory. 4. In 1.5 mM Ca-o(2+) the current-voltage (I-V) relationship of I-cat was S-shaped with a reversal potential (E(r)) of about +9 mV. The I-V characteristics and E(r) of the potentiated current in 200 mu M Ca-o(2+) were not markedly different from those in 1.5 mM Ca-o(2+). 5. During the noradrenaline-induced I-cat removal of external Mg2+ caused a small increase in the amplitude of I-cat which was not as great as that seen on reduction of [Ca2+](o) and there was no facilitatory effect of Mg-o(2+). 6. These results indicate that external Ca2+ has a dual action on I-cat, both facilitating and inhibiting the current. This dual action is not shared with external Mg2+.