The effect of glucagon on the liver cell membrane potential

1. Intracellular recordings of membrane potential were made from superficial cells of isolated mouse liver segments superfused with physiological salt solutions.2. The mean resting cell membrane potential was -39.4 mV.3. Glucagon caused a dose-dependent membrane hyperpolarization which was detectable at 10(-9)M and maximal (7 mV) at 10(-7)M. The hyperpolarization started within half a minute after exposure to glucagon. Secretion (2 x 10(-7)M) had no effect on the membrane potential.4. Adrenaline (10(-6)M) and isoprenaline (10(-6)M) also caused membrane hyperpolarization (4-6 mV). The effect of isoprenaline, but not that of adrenaline, was blocked by propranolol (5 x 10(-6)M).5. Dibutyryl adenosine 3',5'-monophosphate (10(-3)M) caused a membrane hyperpolarization of 4-8 mV.6. In the absence of extracellular K or the presence of Strophanthin-G (10(-3)M) the resting potential was decreased and the response to glucagon reduced. During exposure to a solution containing 20 mM-K the resting potential was slightly enhanced and the amplitude of the glucagon-induced hyperpolarization reduced compared with control conditions.7. It is concluded that the effect of glucagon on the membrane potential is due to an interaction with specific membrane receptors probably leading to activation of the membrane-bound adenyl cyclase. It is probable that the hyperpolarization is mediated by cyclic AMP. The hyperpolarization induced by glucagon is dependent on a normal function of the membrane Na-K pump.