The Journal of Neurophysiology Vol. 86 No. 2 August 2001, pp. 641-650
Copyright ©2001 by the American Physiological Society

Nerve Growth Factor Regulates Sodium But Not Potassium Channel Currents in Sympathetic B Neurons of Adult Bullfrogs

Department of Pharmacology and University Centre for Neuroscience, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

Lei, Saobo, William F. Dryden, and Peter A. Smith. Nerve Growth Factor Regulates Sodium But Not Potassium Channel Currents in Sympathetic B Neurons of Adult Bullfrogs. J. Neurophysiol. 86: 641-650, 2001. The TTX-sensitive and -resistant components of the voltage-gated Na⁺ current (TTX-s I_Na and TTX-r I_Na) are increased within 2 wk of cutting the axons of B-cells in bullfrog paravertebral sympathetic ganglia (BFSG). Axotomy also increases the noninactivating, voltage-activated K⁺ current (M current I_M), whereas delayed rectifier K⁺ current (I_K) is reduced. We found that similar effects were produced when BFSG B cells were dissociated from adult bullfrogs and maintained in a defined-medium, neuron-enriched, low-density, serum-free culture. Thus the density of TTX-s I_Na, TTX-r I_Na, and I_M were transiently increased, whereas I_K density was decreased. Reduction in voltage-sensitive, Ca²⁺-dependent K⁺ current (I_C) was attributed to previously documented decreases in Ca²⁺ channel current (I_Ca). To test whether axotomy- or culture-induced changes in ion channel function reflect loss of retrograde influence of nerve growth factor (NGF), we examined the effect of murine -NGF on TTX-s I_Na, TTX-r I_Na, I_K, and I_M. Culture of neurons for 15 days in the presence of NGF (200 ng/ml), more than doubled total I_Na density but did not enhance neurite outgrowth. The TTX-r I_Na density was increased about threefold and the TTX-s I_Na density increased 2.4-fold. NGF did not affect the activation or inactivation kinetics of the total Na⁺ conductance. Effects of NGF were blocked by the transcription inhibitors, cordycepin (20 µM) and actinomycin D (0.01 µg/ml). I_K and I_M were unaffected by NGF, and although I_C was enhanced, this likely reflected the known effect of NGF on I_Ca in BFSG neurons. Na⁺ channel synthesis and/or expression in adult sympathetic neurons is therefore subject to selective regulation by NGF. Despite this, the increase in I_Na and I_M as well as the decrease in I_K seen in BFSG neurons in culture or after axotomy cannot readily be explained in terms of alterations in the availability of target-derived NGF.