Article date: April 1998
By: Yoshinaka Murai, Hitoshi Ishibashi, Norio Akaike, Yushi Ito, in Volume 123, Issue 7, pages 1441-1449
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.
ACh inhibited the HVA Ca2+ currents in a concentration‐ and voltage‐dependent manner.
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.
Nifedipine, ω‐conotoxin‐GVIA and ω‐conotoxin‐MVIIC reduced the HVA ICa 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.
The ACh‐sensitive current component was markedly reduced in the presence of ω‐conotoxin‐GVIA, but not with both nifedipine and ω‐conotoxin‐MVIIC. ACh also inhibited the R‐type HVA ICa remaining in saturating concentrations of nifedipine, ω‐conotoxin‐GVIA and ω‐conotoxin‐MVIIC.
The inhibitory effect of ACh was prevented by pretreatment with pertussis toxin.
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.
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.
ACh inhibited the HVA Ca2+ currents in a concentration‐ and voltage‐dependent manner.
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.
Nifedipine, ω‐conotoxin‐GVIA and ω‐conotoxin‐MVIIC reduced the HVA ICa 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.
The ACh‐sensitive current component was markedly reduced in the presence of ω‐conotoxin‐GVIA, but not with both nifedipine and ω‐conotoxin‐MVIIC. ACh also inhibited the R‐type HVA ICa remaining in saturating concentrations of nifedipine, ω‐conotoxin‐GVIA and ω‐conotoxin‐MVIIC.
The inhibitory effect of ACh was prevented by pretreatment with pertussis toxin.
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.
British Journal of Pharmacology (1998) 123, 1441–1449; doi:10.1038/sj.bjp.0701753
DOI: 10.1038/sj.bjp.0701753
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