CARBACHOL INHIBITION OF CA2+ CURRENTS IN VENTRICULAR CELLS OBTAINED FROM NEONATAL AND ADULT RATS

We investigated the postnatal developmental changes produced by the mu scarinic receptor agonist, carbachol, on the L-type Ca2+ current (I-Ca (L)) in neonatal (aged 5 to 7 days) and adult (aged 2 to 5 months) rat ventricular cells by using the whole-cell voltage clamp technique. Ca rbachol inhibited the isoproterenol-stimulated I-Ca(L). The maximal in hibition was 89.3 +/- 4.8% (n = 5) in neonatal cells and 17.7 +/- 7.7% (n = 9) in adult cells. Carbachol inhibited the forskolin-stimulated I-Ca(L) to almost same extent as the isoproterenol-stimulated I-Ca(L). In the cells pretreated with pertussis toxin, carbachol failed to inh ibit the isoproterenol-stimulated I-Ca(L), indicating that carbachol p roduced its effect via a pertussis toxin-sensitive G-protein pathway. The effects of carbachol in adult cells became more pronounced, increa sing from 17.7% to 54.8% (n = 11), with the addition of the synthetic inhibitory G-protein alpha subunit (G(i alpha)) (1 mu M) to the reacti on. Conversely, the alpha subunit of another pertussis toxin-sensitive synthetic G-protein (G(o alpha), 1 mu M) failed to mimic the effect o f G(i alpha). These results suggest that, in rat ventricular cells, (1 ) the action of carbachol on I-Ca(L) showed a marked decrease during d evelopment; (2) the decrease in the effect of carbachol in adult cells is in part due to a decrease in the activity of pertussis toxin-sensi tive G protein, especially G(i alpha). (C) 1998 Elsevier Science B.V. All rights reserved.