Rundown of a transient potassium current is attributable to changes in channel voltage dependence

Many ionic currents undergo significant rundown during whole-cell recording. Although rundown is an artifact associated with the recording method, studying the mechanism of rundown may lead to understanding mechanisms regulating channel functions in physiological conditions. The mechanisms for rundown, however, remain obscure for many channels. Here we have studied the mechanism for rundown of an A-type K(+) current in mouse striatal cholinergic interneurons. The interneuron expressed a prominent component of A-type current which exhibited significant rundown during whole-cell recording. When the current was assessed with a highly hyperpolarized prepotential (-140 mV), however, the rundown was virtually fully suppressed, suggesting its being dependent on voltage. Estimation of channel voltage dependence revealed that both activation and inactivation curves shifted towards hyperpolarized potentials during rundown. The shift was suppressed by intracellular ATP, but was affected neither by phosphatase inhibitors nor by antioxidative reagents. The gradual shift of inactivation curve towards negative potentials would make the holding potential progressively inactivate the channel, resulting in apparent loss of activity of the channels. Our results thus provide a biophysical explanation for rundown of A-type current. .