Extrinsic regulation of T‐type Ca2+ channel expression in chick nodose ganglion neurons

AbstractFunctional expression of T‐type Ca2+ 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 Ca2+ channels in vitro. Voltage‐gated Ca2+ 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 Ca2+ channels without any significant effect on HVA currents. T‐type Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ channels. Heart extract‐ or CNTF‐evoked stimulation of T‐type Ca2+ 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 Ca2+ channels. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007