Acetylcholine modulation of high-voltage-activated calcium channels in the neurones acutely dissociated from rat paratracheal ganglia.
1. The modulation of high-voltage-activated (HVA) Ca2+ channels by acetylcholine (ACh) was studied in the paratracheal ganglion cells acutely dissociated from 2-week-old Wistar rats by use of the nystatin perforated patch recording configuration under voltage-clamp conditions. 2. ACh inhibited the HVA Ca2+ currents in a concentration- and voltage-dependent manner. 3. The inhibition was mimicked by a muscarinic agonist, oxotremorine. Pirenzepine and methoctramine produced parallel shifts to the right in the ACh concentration-response curves. Schild analysis of the ACh concentration-ratios yield pA2 values for pirenzepine and methoctramine of 6.85 and 8.57, respectively, suggesting the involvement of an M2 receptor. 4. Nifedipine, omega-conotoxin-GVIA and omega-conotoxin-MVIIC reduced the HVA I(Ca) by 16.8, 59.2 and 6.3%, respectively. 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 component was markedly reduced in the presence of omega-conotoxin-GVIA, but not with both nifedipine and omega-conotoxin-MVIIC. ACh also inhibited the R-type HVA I(Ca) remaining in saturating concentrations of nifedipine, omega-conotoxin-GVIA and omega-conotoxin-MVIIC. 6. The inhibitory effect 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 the M2 muscarinic receptor in paratracheal ganglion cells.
Murai
Y
Y
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ishibashi
H
H
Akaike
N
N
Ito
Y
Y
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005724:Ganglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000166:cytology / Q000294:innervation* / Q000378:metabolism
D015220:Calcium Channels; D018727:Muscarinic Antagonists; D019204:GTP-Binding Proteins; D000109:Acetylcholine