American Journal of Physiology-Heart and Circulatory Physiology · 1999 · 44 citations · 32 references
Life SciencesBiochemistryPharmacologyCell SignalingElectrophysiologySignal TransductionCalcium SignalingCardiac Ion ChannelsIntracellular Calcium SignalingIon Channel RegulationTyrosine Kinase InhibitorsVentricular ElectrophysiologyCalcium Channel ModulatorsCalcium Channel PharmacologyCalcium-dependent Channel RegulationCell ConfigurationCurrent-voltage RelationshipL-type Calcium CurrentTyrosine Kinase InhibitionTyrosine Kinase Receptors
Guinea pig ventricular myocytes in whole cell configuration were treated with tyrosine kinase (TK) inhibitors [genistein (Gst), tyrphostin A23 (T23), and tyrphostin A25 (T25)] and with inactive analogs [daidzein, genistin, and tyrphostin A1 (T1)] to measure effects on L-type Ca2+ current (ICa,L). Gst inhibited ICa,L (IC50 = 47 microM) without affecting its time course or shifting the ICa, L-voltage relationship. At the highest concentration of isoflavone tested (200 microM), ICa,L was inhibited by 66 +/- 7% (Gst), 22 +/- 2% (daidzein), and 1 +/- 3% (genistin). Inhibition of ICa,L by the active tyrphostins was significantly larger than inhibition by T1; at 200 microM the inhibitions were 72 +/- 6% (T23), 71 +/- 6% (T25), and 27 +/- 6% (T1). The phosphotyrosine phosphatase inhibitor orthovanadate (1 mM) had a small stimulatory effect (6 +/- 2%) on basal ICa,L and blocked the inhibition of ICa,L by TK inhibitors. The data suggest a role for the TK-phosphotyrosine phosphatase system in the regulation of cardiac Ca2+ channels.
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Genistein, a specific inhibitor of tyrosine-specific protein kinases.
Tetsu Akiyama, Junko Ishida, Shizue Nakagawa et al. · Journal of Biological Chemistry · 1987 · 3.7K citations · Full text
Regulation of NMDA receptors by tyrosine kinases and phosphatases
Yu Tian Wang, Michael W. Salter · Nature · 1994 · 667 citations