G protein alpha subunit G alpha z couples neurotransmitter receptors to ion channels in sympathetic neurons.
The functional roles subserved by G(alpha)z, a G protein alpha subunit found predominantly in neuronal tissues, have remained largely undefined. Here, we report that G(alpha)z coupled neurotransmitter receptors to N-type Ca2+ channels when transiently overexpressed in rat sympathetic neurons. The G(alpha)z-mediated inhibition was voltage dependent and PTX insensitive. Recovery from G(alpha)z-mediated inhibition was extremely slow but accelerated by coexpression with RGS proteins. G(alpha)z selectively interacted with a subset of receptors that ordinarily couple to N-type Ca2+ channels via PTX-sensitive Go/i proteins. In addition, G(alpha)z rescued the activation of heterologously expressed GIRK channels in PTX-treated neurons. These results suggest that G(alpha)z is capable of coupling receptors to ion channels and might underlie PTX-insensitive ion channel modulation observed in neurons under physiological and pathological conditions.
Jeong
S W
SW
Laboratory of Molecular Physiology, Guthrie Research Institute, Sayre, Pennsylvania 18840, USA.
Ikeda
S R
SR
D000320:Adrenergic Fibers / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005033:Ethylmaleimide / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044385:GTP-Binding Protein alpha Subunits; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020690:GTPase-Activating Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000166:cytology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044385:GTP-Binding Protein alpha Subunits; D020690:GTPase-Activating Proteins; C490963:Gnaz protein, rat; D007473:Ion Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011506:Proteins; D017981:Receptors, Neurotransmitter; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D005033:Ethylmaleimide; D002118:Calcium; D009638:Norepinephrine