MODULATION OF ATP-SENSITIVE POTASSIUM CHANNEL ACTIVITY BY FLASH-PHOTOLYSIS OF CAGED-ATP IN RAT-HEART CELLS

We have used 'caged-ATP' to investigate the kinetic behavior of KATP channels in ventricular cells from rat heart. In whole cells, loaded with 'caged-ATP', an increase of intracellular [ATP] following a UV light flash produced a decrease of KATP channel current that was too slow (τ ≈ 300 ms) to be explained by the expected timecourse of ATP release (τ ≈ 3 ms) and the time-course of channel blockade by ATP (τ ≈ 20 ms). In isolated membrane patches, caged-ATP itself caused partial blockade of KATP channels. Under these conditions, photorelease of ATP caused channel activity to decline further. The results suggest that caged-ATP can bind to the KATP channel but, on binding, decreases the open probability to a lesser extent than does ATP. Additionally, the observations indicate that for photolytically-generated ATP to bind to the channel, caged-ATP must first unbind (slowly) from the channel. We conclude that 'caged-ATP' is not fully caged with respect to its allosteric action on the KATP channel. © 1990 Springer-Verlag.