Abstract
Multiple Components of Ca-activated K currents in mouse pancreatic beta cellsIn beta cells, two types of Ca activated K channels have been described. One component, Kslow, is believed to be mediated by small-conductance, voltage-independent (SK) channels; it is thought to regulate the duration of intervals between successive action-potential bursts observed when beta cells are exposed to moderately elevated glucose. In contrast, the functional role of the second type of Ca activated K channels, the large conductance, Ca- and voltage-activated, BK channels, is not well understood. BK channel subunit genes have been detected in insulin-secreting cell lines, and BK channels have been observed functionally in rodent beta cells; however, early studies with BK channel blocking drugs have failed to identify a role for these channels in the electrical excitability or the stimulus-secretion coupling of beta cells.Using patch clamp recording under quasi-physiological conditions, we show that the BK channel current can contribute up to a half of the outward current activated by depolarizing pulses whose amplitude resembles the voltage excursion of beta cell action potentials. Kinetic and pharmacological experiments reveal that the beta cell BK current consists of several pharmacologically, kinetically, and possibly spatially, distinct components. Our results suggest that the BK current could play a significant role in regulating beta cell electrical excitability of stimulus secretion coupling.
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