Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic Fibers / metabolism*
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Animals
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Calcium / metabolism
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Calcium Channel Blockers / pharmacology
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Calcium Channels / drug effects
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Calcium Channels / metabolism
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Cells, Cultured
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Ethylmaleimide / pharmacology
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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GTP-Binding Protein alpha Subunits*
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / physiology*
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GTPase-Activating Proteins
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Heterotrimeric GTP-Binding Proteins*
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Ion Channels / metabolism*
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Male
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Neurons / metabolism*
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Neurons / physiology
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Norepinephrine / pharmacology
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Potassium Channels, Inwardly Rectifying*
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Proteins / pharmacology
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Rats
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Rats, Wistar
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Receptors, Neurotransmitter / metabolism*
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Superior Cervical Ganglion / cytology
Substances
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Calcium Channel Blockers
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Calcium Channels
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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GTP-Binding Protein alpha Subunits
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GTPase-Activating Proteins
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Gnaz protein, rat
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Ion Channels
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Proteins
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Receptors, Neurotransmitter
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GTP-Binding Proteins
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Heterotrimeric GTP-Binding Proteins
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Ethylmaleimide
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Calcium
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Norepinephrine