Abstract
Modulation of Ca2+ channel activity by protein kinases constitutes one of the major mechanisms regulating neuronal functions. Here, we explored the possible modulation of neuronal Ca2+ channels by protein tyrosine kinases (PTKs). To this end, the effects of PTK inhibitors on whole-cell Ba2+ currents (I Ba) through voltage-gated Ca2+ channels were analysed in differentiated NG108–15 neuroblastoma × glioma hybrid cells. Genistein suppressed I Ba in a concentration-dependent fashion (IC50 = 22 μM). Although daidzein, an analogue of genistein that is devoid of PTK inhibitory activity, also suppressed I Ba, we estimated that specific PTK inhibition by genistein reduced I Ba amplitude by 30%. In addition, lavendustin A (20 μM) and herbimycin A (20 μM), two other distinct PTK inhibitors, depressed I Ba by 22% and 20%, respectively. Genistein suppressed N-type and T-type currents, sparing L-type current, and its effect was independent of G protein activation. The results suggest that the activity of neuronal Ca2+ channels can be modulated by PTKs, opening the possibility that some of the functions of PTKs in the nervous system are mediated by Ca2+ channel modulation.
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Received: 21 November 1997 / Received after revision: 12 January 1998 / Accepted: 13 January 1998
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Morikawa, H., Fukuda, K., Mima, H. et al. Tyrosine kinase inhibitors suppress N-type and T-type Ca2+ channel currents in NG108–15 cells. Pflügers Arch 436, 127–132 (1998). https://doi.org/10.1007/s004240050613
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DOI: https://doi.org/10.1007/s004240050613