Kv1.3 channels in postganglionic sympathetic neurons: expression, function, and modulation.
Kv1.3 channels are known to modulate many aspects of neuronal function. We tested the hypothesis that Kv1.3 modulates the function of postganglionic sympathetic neurons. RT-PCR, immunoblot, and immunohistochemical analyses indicated that Kv1.3 channels were expressed in these neurons. Immunohistochemical analyses indicated that Kv1.3 protein was localized to neuronal cell bodies, processes, and nerve fibers at sympathetic neurovascular junctions. Margatoxin (MgTX), a specific inhibitor of Kv1.3, was used to assess the function of the channel. Electrophysiological analyses indicated that MgTX significantly reduced outward currents [P < 0.05; n = 18 (control) and 15 (MgTX)], depolarized resting membrane potential, and decreased the latency to action potential firing [P < 0.05; n = 11 (control) and 13 (MgTX)]. The primary physiological input to postganglionic sympathetic neurons is ACh, which activates nicotinic and muscarinic ACh receptors. MgTX modulated nicotinic ACh receptor agonist-induced norepinephrine release (P < 0.05; n >or= 6), and MgTX-sensitive current was suppressed upon activation of muscarinic ACh receptors with bethanechol (P < 0.05; n = 12). These data indicate that Kv1.3 affects the function of postganglionic sympathetic neurons, which suggests that Kv1.3 influences sympathetic control of cardiovascular function. Our data also indicate that modulation of Kv1.3 is likely to affect sympathetic control of cardiovascular function.
Doczi
Megan A
MA
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Morielli
Anthony D
AD
Damon
Deborah H
DH
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012604:Scorpion Venoms / Q000494:pharmacology; D017779:Sympathetic Fibers, Postganglionic / Q000378:metabolism / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D014162:Transfection
D051664:Kv1.3 Potassium Channel; D012604:Scorpion Venoms; D049452:Green Fluorescent Proteins; C077910:margatoxin