Inhibition of N- and L-type calcium channels by muscarinic receptor activation in rat sympathetic neurons.
Modulation of N- and L-type Ca2+ channels by oxotremorine-M (oxo-M) acting on muscarinic receptors and norepinephrine (NE) acting on alpha-adrenergic receptors was studied in superior cervical ganglion neurons. Oxo-M depresses dihydropyridine-augmented tail currents in whole-cell recordings, whereas NE does not. This modulation of L-type Ca2+ channels by oxo-M is abolished by adding 20 mM BAPTA to the pipette solution. Oxo-M, acting via a diffusible messenger, reduces the probability of opening of single N- and L-type channels recorded in cell-attached patches. We conclude that a diffusible messenger signaling pathway activated by oxo-M inhibits both N- and L-type Ca2+ channels, whereas a membrane-delimited pathway activated by oxo-M and NE inhibits only N-type Ca2+ channels.
Mathie
A
A
Department of Physiology and Biophysics, University of Washington, Seattle 98195.
Bernheim
L
L
Hille
B
B
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004553:Electric Conductivity; D005728:Ganglia, Sympathetic / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D004095:Dihydropyridines; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D010095:Oxotremorine; C042743:oxotremorine M; C038806:1,4-dihydropyridine; D009638:Norepinephrine