Modulation of volume-sensitive chloride current by noradrenaline in rabbit portal vein myocytes

The effect of noradrenaline on the volume-sensitive chloride current was studied with conventional whole-cell recording techniques in freshly dispersed isolated smooth muscle cells of the rabbit portal vein. In the absence of receptor antagonists, noradrenaline produced an increase in the amplitude of I-Cl(swell) in some cells and a decrease in others. In the presence of the beta-adrenoceptor antagonist propranolol, noradrenaline increased I-Cl(swell) and in the presence of the alpha(1)-adrenoceptor antagonist prazosin, noradrenaline reduced I-Cl(swell). The phospholipase C (PLC) inhibitor U73122 reduced the amplitude of I-Cl(swell) whereas the inactive analogue U73343 had no effect. The phorbol esters phorbol-12-myristate-13-acetate (PMA) and phorbol-12,13-dibutyrate (PDBu) increased the amplitude of I-Cl(swell) by approximately 60 and 100%, respectively, in a voltage-independent fashion. Inhibitors of protein kinase C (PKC) chelerythrine and calphostin-C decreased the amplitude of I-Cl(swell) in a concentration-dependent but voltage-independent manner. Bath application of 8-Br-cAMP decreased I-Cl(swell) by about 60% whereas the inhibitor of protein kinase A (PKA) KT5720 increased the amplitude of I-Cl(swell) by approximately 80-90%. In the presence of propranolol, chelerythrine prevented the increase of I-Cl(swell) by noradrenaline; in the presence of prazosin, KT5720 blocked the inhibitory action of noradrenaline. The results show that in rabbit portal vein myocytes noradrenaline enhances I-Cl(swell) by acting on alpha(1)-adrenoceptors and reduces I-Cl(swell) by stimulating beta-adrenoceptors. The data suggest that the potentiating and inhibitory effects of noradrenaline are mediated, respectively, by PKC and PKA.