[Coupling of muscarinic acetylcholine receptors, m1/m3 and m2/m4, to phosphoinositide metabolism and Ca2+ channels in DNA-transfected NG108-15 cells].
The muscarinic acetylcholine receptor (mAChR) is an integral membrane protein that transduces stimulus to effectors through the activation of guanine nucleotide-binding (G) proteins. Four or more subtypes of mAChR were detected in various tissues, and their primary structures were elucidated by cloning and sequence analysis of complementary DNA. Functional differences between them existed when they were expressed in clonal culture cells. mAChRI (m1) and mAChRIII (m3) preferentially activated phosphoinositide (PI) hydrolysis and opened Ca(2+)-activated K+ channels followed by closure of the M (K+)-currents, while such current activities were rarely evoked by mAChRII (m2)- and mAChRIV (m4)-transformed cells. Although it has been reported that mAChRII and mAChRIV inhibited adenylate cyclase, there was little or no such inhibition by mAChRI and mAChRIII. It is known that heart and neuronal mAChR modulate voltage-sensitive Ca2+ currents, but which species of mAChR subtypes are involved has been poorly understood. Recently we identified that endogenous mAChRIV and exogenous mAChRII expressed in NG108-15 neuroblastoma-glioma hybrid cells, but not mAChRI and mAChRIII, efficiently depressed high-threshold Ca2+ currents in a pertussis toxin-sensitive manner.
Higashida
H
H
Department of Biophysics, Kanazawa University School of Medicine, Japan.
Noda
M
M
Kimura
Y
Y
Hashii
M
M
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D015220:Calcium Channels; D007473:Ion Channels; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic