An adenosine triphosphate (ATP)-sensitive K+ channel of rat neocortical neurons is bi-gated by intracellular ATP and voltage: a novel channel gating mechanism?

To determine whether the adenosine triphosphate (ATP)-sensitive K+ (K-ATP) channels, which are suggested to be mainly regulated by intracellular ATP or other kinds of triphosphate nucleotides, are gated by membrane potentials (Vm), single K-ATP channel currents were studied on inside-out membrane patches of neurons acutely dissociated from Sprague-Dawley rat neocortex. The K-ATP channels recorded have a unitary conductance from 96.97 +/- 5.32 pS (n = 11) at potentials of approximately 10-60 mV to 98.31 +/- 3.26 pS (n = 11) at approximately -10 to -60 mV. Besides being inhibited by cytoplasmic ATP, channel kinetics was also affected by Vm. Open- and closed-time histograms were well fitted by 2 exponentials, suggesting that the channels have 2 open and closed states. Mean open time (tau om), open probability increased while mean closed time (tau cm) decreased with depolarization. The fitted equations of the relationships between Vm and those kinetic parameters may be described as: tau om = -159.26lnV + 403.64, Po = -0.01Vm2 + 0.08Vm + 0.87 and tau cm = 0.17Vm3-2.5Vm2 + 10.35Vm - 7.68, respectively. We suggest that the K-ATP channels be bi-gated by both intracellular ATP and membrane potentials. This property of the neuronal K-ATP channels may be related to their pathophysiological functions.