Abstract
The ATP-sensitive potassium (K(ATP)) channel is named after its characteristic inhibition by intracellular ATP. The inhibition is a centerpiece of how the K(ATP) channel sets electrical signaling to the energy state of the cell. In the beta cell of the endocrine pancreas, for example, ATP inhibition results from high blood glucose levels and turns on electrical activity leading to insulin release. The underlying gating mechanism (ATP inhibition gating) includes ATP stabilization of closed states, but the action of ATP on the open state of the channel is disputed. The original models of ATP inhibition gating proposed that ATP directly binds the open state, whereas recent models indicate a prerequisite transition from the open to a closed state before ATP binds and inhibits activity. We tested these two classes of models by using kinetic analysis of single-channel currents from the cloned mouse pancreatic K(ATP) channel expressed in Xenopus oocytes. In particular, we combined gating models based on fundamental rate law and burst gating kinetic considerations. The results demonstrate open-state ATP dependence as the major mechanism by which ATP speeds exit from the active burst state underlying inhibition of the K(ATP) channel by ATP.
Highlights
The ATP-sensitive potassium (KATP)* channel couples electrical activity to metabolism in a variety of cells, and plays an important physiological role (Noma, 1983; Ashcroft et al, 1984; Cook and Hales, 1984; Jovanovic et al, 1998; Aguilar-Bryan and Bryan, 1999)
We studied ligand-dependent and independent gating transitions from the open state of the wild-type mouse pancreatic KATP channel expressed in Xenopus oocytes
Because the burst comprises the open and fast closed states, the results indicate that the decrease in burst duration by ATP involves solely the open state
Summary
The ATP-sensitive potassium (KATP)* channel couples electrical activity to metabolism in a variety of cells, and plays an important physiological role (Noma, 1983; Ashcroft et al, 1984; Cook and Hales, 1984; Jovanovic et al, 1998; Aguilar-Bryan and Bryan, 1999). In the  cell of the endocrine pancreas, only a handful of active KATP channels out of hundreds suffices to prevent cell electrical activity when energy is low, and closure of these few channels when energy is high initiates electrical signaling leading to insulin secretion (Cook et al, 1988). The need for such complete inhibition of the active states of the KATP channel suggests that multiple inhibitory mechanisms might be at work.
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