ACETYLCHOLINE MODULATION OF HIGH-VOLTAGE-ACTIVATED CALCIUM CHANNELS IN THE NEURONS ACUTELY DISSOCIATED FROM RAT PARATRACHEAL GANGLIA

1 The modulation of high-voltage-activated (HVA) Ca2+ channels by acet ylcholine (ACh) was studied in the paratracheal ganglion cells acutely dissociated from 2-week-old Wistar rats by use of the nystatin perfor ated patch recording configuration under voltage-clamp conditions. 2 A Ch inhibited the HVA Ca2+ currents in a concentration- and voltage-dep endent manner. 3 The inhibition was mimicked by a muscarinic agonist, oxotremorine. Pirenzepine and methoctramine produced parallel shifts t o the right in the ACh concentration-response curves. Schild analysis of the ACh concentration-ratios yield pA(2) values for pirenzepine and methoctramine of 6.85 and 8.57, respectively, suggesting the involvem ent of an M-2 receptor. 4 Nifedipine, omega-conotoxin-GVIA and omega-c onotoxin-MVIIC reduced the HVA I-Ca by 16.8, 59.2 and 6.3%, respective ly. A current insensitive to all of these Ca2+ antagonists, namely 'R- type', was also observed. The results indicated the existence of L-, N -, P/Q-, and R-type Ca2+ channels. 5 The ACh-sensitive current compone nt was markedly reduced in the presence of omega-conotoxin-GVIA, but n ot with both nifedipine and omega-conotoxin-MVIIC. ACh also inhibited the R-type HVA I-Ca remaining in saturating concentrations of nifedipi ne, omega-conotoxin-GVIA and omega-conotoxin-MVIIC. 6 The inhibitory e ffect of ACh was prevented by pretreatment with pertussis toxin. 7 It was concluded that ACh selectively reduces both the N- and R-type Ca2 channels, by activating pertussis toxin sensitive G-protein through t he M-2 muscarinic receptor in paratracheal ganglion cells.