Figure 3. Tyrosine kinase inhibitors activate KATP channel currents.
A, current clamp record of a cell dialysed with an electrode solution containing 5 mM ATP. Application of daidzein (10 μM) had no effect on the resting membrane potential of the cell. B, top panel: current clamp trace of a cell dialysed with 5 mM ATP. Addition of genistein (10 μM) resulted in hyperpolarization of the cell membrane to −80 mV. The sulphonylurea tolbutamide (100 μM) completely reversed the genistein-induced hyperpolarization to pre-genistein levels. Bottom panel: plot of the current-voltage relationships for the voltage clamped currents shown at the top: ○, control; •, genistein; ▴, genistein and tolbutamide. The genistein-induced hyperpolarization was accompanied by an increase in K+ conductance. Tolbutamide readily reversed this action of genistein with a reversal potential of −77 mV. C, current clamp record of a CRI-G1 cell dialysed with 5 mM ATP. Application of tyrphostin 1 (10 μM) for at least 25 min failed to affect the resting membrane potential of the cell. D, top panel: current clamp record of a cell dialysed with 5 mM ATP. Application of tyrphostin B42 (10 μM) resulted in hyperpolarization of the CRI-G1 cell to −78 mV. Tolbutamide (100 μM) completely reversed the tyrphostin-induced hyperpolarization to pre-tyrphostin levels. Bottom panel, plot of the current- voltage relationships for the points specified in the top panel: ▴, control; •, tyrphostin B42; ○, tyrphostin B42 and tolbutamide. Tyrphostin B42 increased the membrane conductance relative to control and tolbutamide reversed this action of tyrphostin with a reversal potential of −83 mV.