Bursting Electrical Activity Generated in the Presence of K_ATP Channel Blockers

Abstract

The use of the patch-clamp technique has made possible the characterization of the glucose sensitivity of a number of cation channels present in the β-cell membrane. One of these channels, the ATP-dependent K⁺ (K_ATP) channel, is specifically blocked by intracellular ATP and appears to play an essential role in the coupling of glucose metabolism to membrane depolarization and, hence, to Ca²⁺ influx and to the initiation of insulin release^[1]. The available data indicate that the activity of the K_ATP channel is almost fully suppressed at 6 mM glucose, ie. a concentration which brings the membrane potential to a level just below the threshold for the appearance of electrical activity. At glucose concentrations above 7 mM the β-cell displays a pattern of bursting electrical activity which is remarkably sensitive to the hexose concentration, with the silent unexcited period (“silent phase”) being progressively reduced and the depolarized active phase (“active phase”) becoming progressively elongated as the size of the glucose stimulus increases^[2]. We conclude that, while the glucose-mediated reduction in the activity of the K_ATP channels is indeed essential for the glucose-evoked initial depolarization of the β-cell, the modulation of bursting electrical activity by the hexose in the range 7–20 mM is apparently accounted for, at least in part, by a channel distinct from the K_ATP channel. The present account aims at providing evidence to support this hypothesis.