HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 99/3/1319    most recent 00966.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ford, C. P. Articles by Smith, P. A. PubMed PubMed Citation Articles by Ford, C. P. Articles by Smith, P. A.

Differential Neurotrophic Regulation of Sodium and Calcium Channels in an Adult Sympathetic Neuron

Centre for Neuroscience and Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada

Submitted 27 August 2007; accepted in final form 19 January 2008

Adult neuronal phenotype is maintained, at least in part, by the sensitivity of individual neurons to a specific selection of neurotrophic factors and the availability of such factors in the neurons' environment. Nerve growth factor (NGF) increases the functional expression of Na⁺ channel currents (I_Na) and both N- and L-type Ca²⁺ currents (I_Ca,N and I_Ca,L) in adult bullfrog sympathetic ganglion (BFSG) B-neurons. The effects of NGF on I_Ca involve the mitogen-activated protein kinase (MAPK) pathway. Prolonged exposure to the ganglionic neurotransmitter luteinizing hormone releasing hormone (LHRH) also increases I_Ca,N but the transduction mechanism remains to be elucidated as does the transduction mechanism for NGF regulation of Na⁺ channels. We therefore exposed cultured BFSG B-neurons to chicken II LHRH (0.45 µM; 6–9 days) or to NGF (200 ng/ml; 9–10 days) and used whole cell recording, immunoblot analysis, and ras or rap-1 pulldown assays to study effects of various inhibitors and activators of transduction pathways. We found that 1) LHRH signals via ras-MAPK to increase I_Ca,N, 2) this effect is mediated via protein kinase C-β (PKC-β-II), 3) protein kinase A (PKA) is necessary but not sufficient to effect transduction, 4) NGF signals via phosphatidylinositol 3-kinase (PI3K) to increase I_Na, and 5) long-term exposure to LHRH fails to affect I_Na. Thus downstream signaling from LHRH has access to the ras-MAPK pathway but not to the PI3K pathway. This allows for differential retrograde and anterograde neurotrophic regulation of sodium and calcium channels in an adult sympathetic neuron.