title: The Cav3-Kv4 complex acts as a calcium sensor to maintain inhibitory charge transfer during extracellular calcium fluctuations.
abstract: Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca](o)), yet repetitive synaptic input is known to decrease [Ca](o) in numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca](o) by up to 0.4 mm in the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in an in vitro slice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca](o) on the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Ca(v)3-K(v)4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca]o by dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Ca(v)3-K(v)4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca](o), providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity.
authors: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors: Dustin
authors: D
authors: Anderson
authors: Jordan D T
authors: JD
authors: Engbers
authors: N Colin
authors: NC
authors: Heath
authors: Theodore M
authors: TM
authors: Bartoletti
authors: W Hamish
authors: WH
authors: Mehaffey
authors: Gerald W
authors: GW
authors: Zamponi
authors: Ray W
authors: RW
authors: Turner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010721:Phosphinic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000906:Antibodies; C417736:CAV3 protein, human; D051244:Caveolin 3; D018683:Excitatory Amino Acid Agents; D018756:GABA Antagonists; D051605:Kv Channel-Interacting Proteins; D010721:Phosphinic Acids; D010880:Piperidines; D011412:Propanolamines; D011720:Pyrazoles; D051672:Shal Potassium Channels; D049452:Green Fluorescent Proteins; C085075:CGP 55845A; C103505:AM 251; D002118:Calcium
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