FIGURE 4.

A: at low glucose, high K_ATP channel activity (thick black arrow) keeps the β-cell membrane potential negative, and depolarizing conductances (narrow red arrow) are too small to have a major impact. B: at high glucose, K_ATP channel activity is strongly reduced, and depolarizing currents (even small ones) will exert a stronger effect on the membrane potential. C: the input resistance (R) of the β-cell membrane determines the ease with which electrical activity can be initiated. When K_ATP channel activity is high, R is low. Conversely, when the K_ATP channels are shut, R is high. From Ohm's Law ($V=R·I$), it is evident that the same magnitude of current (I) will produce a much greater change in membrane potential (ΔV) when R is high (red trace) than when it is low (black trace). At high glucose, a small current may depolarize the β-cell sufficiently to trigger action potential firing (dotted red line). The ‟tug-of-warˮ between repolarizing and depolarizing membrane currents explains why potentiators of insulin secretion such as acetylcholine and arginine, which activate small depolarizing currents, are ineffective in the absence of glucose, when the activity of the K_ATP channels is high (i.e., R is low), but are able to stimulate electrical activity and insulin secretion at glucose concentrations that shut most K_ATP channels (i.e., R is high).