A Calcium-Dependent Chloride Current in Insulin-Secreting βTC-3 Cells

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Ca2+-dependent conductances have been hypothesized to play a role in the bursting pattern of electrical activity of insulin-secreting β cells in response to high plasma glucose. A Maxi K+ channel has received the most attention, while a low-conductance Ca2+-activated K+ current has also been identified. We used an increasingly popular β cell model system, the βTC-3 cell line, and the perforated-patch technique to describe the properties of a novel Ca2+-dependent Cl current [I Cl(Ca)] in insulin-secreting pancreatic β cells. The reported ICl(Ca) could be activated under physiological Ca2+ concentrations and is the first of its kind to be described in pancreatic insulin-secreting cells. We found that long depolarizing steps above –20 mV elicited an outward current which showed slow inward relaxation upon repolarization to negative membrane potentials. Both the outward currents and the inward tails showed dependence on Ca2+ influx: their current/voltage (I/V) relations followed that of the ”L-like” Ca2+ current (I Ca) present in these cells; they were blocked completely by the removal of external Ca2+ or application of Cd2+ at concentrations sufficient for complete block of I Ca; and their magnitude increased with the depolarizing step duration. Moreover, the inward tail decayed monoexponentially with a time constant which at voltages negative to activation of I Ca showed a weak linear voltage dependence, while at voltages positive to activation of I Ca it followed the voltage dependence of I Ca. This Ca2+-dependent current reversed at –21.5 mV and when the external Cl concentration was reduced from 159 mM to 62 mM the reversal potential shifted by ≈+20 mV as predicted by the Nernst relation for a Cl-selective current. Cl channel blockers such as DIDS (100 μM) and niflumic acid (100 μM) blocked this current. We concluded that this current was a Ca2+-dependent Cl current [I Cl(Ca)]. From substitution of the external Cl with various monovalent anions and from the reversal potentials we obtained the following permeability sequence for I Cl(Ca): I –>NO3–>Br>Cl>Acetate.