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 non-selective cation current (Icat) 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 microM during stimulation of Icat produced a sustained potentiation of Icat, which indicates an inhibitory action of Cao2+. With 'test' concentrations lower than 100 microM Cao2+ the amplitude of Icat was initially potentiated and then the current subsequently declined. Under these conditions re-addition of 1.5 mM Cao2+ transiently activated Icat which demonstrates an additional facilitatory action of [Ca2+]o. The half-maximal [Ca2+]o for the facilitatory and inhibitory action on Icat was 6 and 400 microM, respectively. 3. When [Ca2+]o was decreased to very low levels (< 10 nM) by inclusion of 1 mM BAPTA in nominally Ca(2+)-free external solution, Icat could still be evoked by noradrenaline. This suggested that Ca2+ is not obligatory for activation of Icat but merely modulatory. 4. In 1.5 mM Cao2+ the current-voltage (I-V) relationship of Icat was S-shaped with a reversal potential (Er) of about +9 mV. The I-V characteristics and Er of the potentiated current in 200 microM Cao2+ were not markedly different from those in 1.5 mM Cao2+. 5. During the noradrenaline-induced Icat, removal of external Mg2+ caused a small increase in the amplitude of Icat which was not as great as that seen on reduction of [Ca2+]o and there was no facilitatory effect of Mgo2+. 6. These results indicate that external Ca2+ has a dual action on Icat, both facilitating and inhibiting the current. This dual action is not shared with external Mg2+.
Helliwell
R M
RM
Department of Pharmacology, St George's Hospital Medical School, London, UK.
Large
W A
WA
D000818:Animals; D000838:Anions / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002414:Cations, Monovalent / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011169:Portal Vein / Q000502:physiology*; D011817:Rabbits
D000838:Anions; D002414:Cations, Monovalent; D007473:Ion Channels; D004533:Egtazic Acid; D008274:Magnesium; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D009638:Norepinephrine