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 MAPkinase pathway. Prolonged exposure to the ganglionic neurotransmitter, LHRH (luteinizing hormone releasing hormone) 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 (0.45µM; 6-9d) or to NGF (200ng/ml; 9-10d) 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-MAP Kinase to increase I_Ca,N, 2) this effect is mediated via protein kinase C--II(PKC--II) 3) Protein kinase A (PKA) is necessary but not sufficient to effect transduction 4) NGF signals via phosphatidylinositol 3 kinase (PI 3 kinase) 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-MAP kinase pathway but not to the PI3 kinase pathway. This allows for differential retrograde and anterograde neurotrophic regulation of sodium and calcium channels in an adult sympathetic neuron.