Muscarinic M-current inhibition via G alpha q/11 and alpha-adrenoceptor inhibition of Ca2+ current via G alpha o in rat sympathetic neurones.
1. Microinjection of selective antibodies into superior cervical ganglion (SCG) neurones has identified the G-protein alpha-subunits mediating muscarinic receptor inhibition of M-type K+ current (IK(M)) and alpha-adrenoceptor inhibition of Ca2+ current (ICa). 2. Antibodies specific for G alpha q/11, but not those for G alpha o, reduced M-current inhibition by the muscarinic agonist oxotremorine-M, whereas anti-G alpha o antibodies, but not anti-G alpha q/11 or anti-G alpha i1-3 antibodies, reduced calcium current inhibition by noradrenaline. 3. Immunoblots with specific anti-G-protein antibodies demonstrated the presence of both G alpha q and G alpha 11, while G alpha o1 (but virtually no G alpha o2) was present. 4. We conclude that M1 muscarinic receptor inhibition of IK(M) is transduced by G alpha q and/or G alpha 11, and that G alpha o transduces alpha-adrenoceptor inhibition of ICa.
Caulfield
M P
MP
Wellcome Laboratory for Molecular Pharmacology, Department of Pharmacology, University College London.
Jones
S
S
Vallis
Y
Y
Buckley
N J
NJ
Kim
G D
GD
Milligan
G
G
Brown
D A
DA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000276:immunology / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000145:classification / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000906:Antibodies; D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D002118:Calcium