Fast inhibition of inwardly rectifying K+ channels by multiple neurotransmitter receptors in oligodendroglia.
An essential function of myelinating oligodendroglia in the mammalian central nervous system is the regulation of extracellular potassium levels by means of a prominent inwardly rectifying K+ current. Cardiac and neuronal K+ inward rectifiers are either activated by hyperpolarizing voltages or controlled by neurotransmitters through the action of receptor-activated G proteins. Neuromodulation of inward rectifiers has not previously been considered as a way to regulate oligodendrocyte function. Here we report the expression of serotonin, somatostatin and muscarinic acetylcholine G protein-coupled receptors in rat brain oligodendrocytes. Activation of these receptors leads to pertussis toxin-sensitive inhibition of inwardly rectifying K+ channels within < 1 s. By contrast, in the heart and in neurons, similar pathways activate an inwardly rectifying conductance. Thus, transmitter-mediated blockade of inward rectifiers appears to be an oligodendrocyte-specific variation of a common motif for convergent signalling pathways. In vivo, expression of this mechanism, which may be dependent on neuron-glia signalling, may have a regulatory role in K+ homeostasis during neuron activity in the central nervous system.
Karschin
A
A
Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
Wischmeyer
E
E
Davidson
N
N
Lester
H A
HA
D000818:Animals; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D017981:Receptors, Neurotransmitter; D019204:GTP-Binding Proteins