Extrinsic regulation of T-type Ca(2+) channel expression in chick nodose ganglion neurons.
Functional expression of T-type Ca(2+) channels is developmentally regulated in chick nodose neurons. In this study we have tested the hypothesis that extrinsic factors regulate the expression of T-type Ca(2+) channels in vitro. Voltage-gated Ca(2+) currents were measured using whole-cell patch clamp recordings in E7 nodose neurons cultured under various conditions. Culture of E7 nodose neurons for 48 h with a heart extract induced the expression of T-type Ca(2+) channels without any significant effect on HVA currents. T-type Ca(2+) channel expression was not stimulated by survival promoting factors such as BDNF. The stimulatory effect of heart extract was mediated by a heat-labile, trypsin-sensitive factor. Various hematopoietic cytokines including CNTF and LIF mimic the stimulatory effect of heart extract on T-type Ca(2+) channel expression. The stimulatory effect of heart extract and CNTF requires at least 12 h continuous exposure to reach maximal expression and is not altered by culture of nodose neurons with the protein synthesis inhibitor anisomycin, suggesting that T-type Ca(2+) channel expression is regulated by a posttranslational mechanism. Disruption of the Golgi apparatus with brefeldin-A inhibits the stimulatory effect of heart extract and CNTF suggesting that protein trafficking regulates the functional expression of T-type Ca(2+) channels. Heart extract- or CNTF-evoked stimulation of T-type Ca(2+) channel expression is blocked by the Jak/STAT and MAP kinase blockers, AG490 and U0126, respectively. This study provides new insights into the electrical differentiation of placode-derived sensory neurons and the role of extrinsic factors in regulating the functional expression of Ca(2+) channels.
Pachuau
Judith
J
Department of Biology, University of Vermont, Burlington, VT 05405, USA.
Martin-Caraballo
Miguel
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000494:pharmacology*; D009206:Myocardium / Q000737:chemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology; D013997:Time Factors
D000906:Antibodies; D020747:Calcium Channels, T-Type; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D011725:Pyridines; D006493:Heparin; C093642:SB 203580