| 9560456 |
Morikawa H, Fukuda K, Mima H, Shoda T, Kato S, Mori K: Tyrosine kinase inhibitors suppress N-type and T-type Ca2+ channel currents in NG108-15 cells. Pflugers Arch. 1998 Jun;436(1):127-32.
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 (IBa) through voltage-gated Ca2+ channels were analysed in differentiated NG108-15 neuroblastoma x glioma hybrid cells. Genistein suppressed IBa in a concentration-dependent fashion (IC50 = 22 microM). Although daidzein, an analogue of genistein that is devoid of PTK inhibitory activity, also suppressed IBa, we estimated that specific PTK inhibition by genistein reduced IBa amplitude by 30%. In addition, lavendustin A (20 microM) and herbimycin A (20 microM), two other distinct PTK inhibitors, depressed IBa 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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