Résumé
* 1 The effects of zinc (Zn super(2+)) on excitability and ionic conductances were analysed on RINm5F insulinoma cells under whole-cell and outside-out patch-clamp recording conditions. * 2 We found that extracellular application of 10-20 mu M Zn super(2+) induced a reversible abolition of Ca super(2+) action potential firing, which was accompanied by an hyperpolarisation of the resting membrane potential. * 3 Higher concentrations of Zn super(2+), in the tens to hundreds micromolar range, induced a reversible reduction of voltage-gated Ca super(2+) and, to a lesser extent, K super(+) currents. Low-voltage-activated Ca super(2+) currents were more sensitive to Zn super(2+) block than high voltage-activated Ca super(2+) currents. * 4 The Zn super(2+)-induced hyperpolarisation arose from a dose-dependent increase in a voltage-independent K super(+) conductance that was pharmacologically identified as an ATP-sensitive K super(+) (K sub(ATP)) conductance. The effect was rapid in onset, readily reversible, voltage independent, and related to intracellular ATP concentration. In the presence of 1 mM intracellular ATP, half-maximal activation of K sub(ATP) channels was obtained with extracellular application of 1.7 mu M Zn super(2+). * 5 Single channel analysis revealed that extracellular Zn super(2+) increased the K sub(ATP) channel open-state probability with no change in the single channel conductance. * 6 Our data support the hypothesis that Zn super(2+) binding to K sub(ATP) protein subunits results in an activation of the channels, therefore regulating the resting membrane potential and decreasing the excitability of RINm5F cells. Taken together, our results suggest that Zn super(2+) can influence insulin secretion in pancreatic beta -cells through a negative feedback loop, involving both K sub(ATP) and voltage-gated conductances.