Apamin-sensitive Ca(2+)-activated K+ channels regulate pacemaker activity in nigral dopamine neurons.
Mesencephalic dopamine-containing neurons exhibit a Ca(2+)-dependent oscillation in membrane potential believed to underlie the ability of these cells to maintain spontaneous activity in the absence of afferent synaptic drive. In the present series of experiments, sharp electrode intracellular recording techniques were used in conjunction with an in vitro brain slice preparation to explore the ionic mechanisms underlying rhythmogenesis in nigral dopamine neurons in the rat. Our results indicate that the K+ channel producing the prolonged post-spike afterhyperpolarization exhibited by these neurons is also principally responsible for generating the falling phase of the autogenous pacemaker oscillation. Alterations in the expression of this conductance are associated with marked changes in neuronal firing pattern, indicating that modulation of ligand-gated Ca(2+)-activated K+ channels may constitute a functional means of altering temporal coding among the major mesotelencephalic dopamine systems.
Ping
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Maryland Psychiatric Research Center, Baltimore 21228, USA.
Shepard
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D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D001030:Apamin; D013779:Tetrodotoxin; D002118:Calcium; D004298:Dopamine