Differential neurotrophic regulation of sodium and calcium channels in an adult sympathetic neuron.
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 Ca(2+) 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 microM; 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-beta (PKC-beta-IotaIota), 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.
Ford
Christopher P
CP
Centre for Neuroscience and Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Wong
Kenneth V
KV
Lu
Van B
VB
Posse de Chaves
Elena
E
Smith
Peter A
PA
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009930:Organic Chemicals / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D011892:Rana catesbeiana; D015398:Signal Transduction / Q000187:drug effects; D015222:Sodium Channels / Q000502:physiology*; D013997:Time Factors; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D009930:Organic Chemicals; C466090:PD 98058; D010703:Phorbol Esters; D015222:Sodium Channels; D007987:Gonadotropin-Releasing Hormone; D020928:Mitogen-Activated Protein Kinases; D020827:rap1 GTP-Binding Proteins