Rabies virus infection prevents the modulation by alpha(2)-adrenoceptors, but not muscarinic receptors, of Ca2+ channels in NG108-15 cells

In mouse neuroblastoma x rat glioma hybrid (NG108-15) cells, we examined wh ether rabies virus infection affects the voltage-dependent Ca2+ current(I-C a) and agonist-induced I-Ca inhibition. The viral infection had little effe ct on the current-voltage relationship for peak I-Ca or on the late I-Ca th at remained at the end of a 200-ms step depolarization. Noradrenaline and c arbachol, via alpha(2)-adrenoceptors and muscarinic receptors, respectively , reduced I-Ca concentration dependently. The maximum effect of noradrenali ne was attained at 10 mu M with 19.4 +/- 1.8% inhibition of I-Ca, which was significantly decreased to 9.9 +/- 1.3% after viral infection. The decreas e was not reversed with 100 mu M noradrenaline, suggesting that it does not result from a decrease in agonist sensitivity of cells. The maximum effect of carbachol (300 mu M; 27.7 +/- 2.9% inhibition) remained unchanged, desp ite carbachol sharing intracellular signaling pathways with noradrenaline. These results indicate that in NG108-15 cells, rabies virus infection does not alter the functional expression of voltage-dependent Ca2+ channels, but it attenuates the alpha(2)-adrenoceptor-mediated I-Ca inhibition, possibly through some change at the receptor level. (C) 2000 Elsevier Science B.V. All rights reserved.