Differential neurotrophic regulation of sodium and calcium channels in an adult sympathetic neuron

作者：Ford Christopher P; Wong Kenneth V; Lu Van B; de Chaves Elena Posse; Smith Peter A^*

来源：Journal of Neurophysiology, 2008, 99(3): 1319-1332.

DOI：10.1152/jn.00966.2007

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,I-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,I-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 mu M; 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,I-N, 2) this effect is mediated via protein kinase C-beta (PKC-beta-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.

• 出版日期2008-3