Isoprenaline- and noradrenaline-induced hyperpolarization of guinea-pig liver cells.

1 Effects of pretreatment with isoprenaline (Isop) or noradrenaline (NA) and various ionic environments on the NA-induced or Isop-induced hyperpolarization of guinea-pig liver cells were investigated by means of a microelectrode technique.2 NA (5.9 x 10(-6) M) decreased the membrane resistance, and hyperpolarized the membrane with or without generation of an initial transient small depolarization. The NA-induced initial depolarization was not dependent on the membrane potential and was increased by Isop (4.0 x 10(-6) M) or glucagon (10(-7) M).3 In Ca-free solution, the NA-induced hyperpolarization became transient and a continuous depolarization followed in the presence of NA. Repetitive application of NA resulted in a complete disappearance of the NA-induced hyperpolarization and was replaced by a slowly developing depolarization with or without generation of the initial transient depolarization. In excess [Ca](o), the NA or Isop-induced hyperpolarization was increased.4 Both Isop and glucagon hyperpolarized the membrane and decreased the membrane resistance, to various degrees. Repetitive application of Isop or glucagon resulted in the disappearance of both Isop and glucagon-induced hyperpolarizations. Pretreatment with NA not only resulted in a recovery of both Isop and glucagon-induced hyperpolarizations, but also extensively enhanced the hyperpolarization.5 After pretreatment with Isop, the NA-induced hyperpolarization was decreased in amplitude and duration and was followed by a slowly developing depolarization. After repetitive application of Isop, NA produced only depolarization of the membrane, and in these conditions, Isop, glucagon or ATP also depolarized the membrane. These depolarizations were reversed to hyperpolarizations by pretreatment with excess [Ca](o).6 After treatment with Na-deficient solution, NA depolarized the membrane and decreased the membrane resistance. Excess [Ca](o) restored the NA-induced membrane response from one of depolarization to one of hyperpolarization.7 In the presence of tetraethylammonium 10mM, the NA-induced hyperpolarization became transient or ceased and depolarization occurred with a reduction in the membrane resistance.8 It is postulated that both NA and Isop increase the free [Ca](i) by releasing bound Ca from storage sites and consequently an increase in K conductance follows. NA but not Isop promotes Ca-influx which replenishes the storage site. In Ca-depleted conditions, NA does not elevate the free [Ca](i) to a threshold concentration required for hyperpolarization, probably because NA induces a small release of Ca from storage sites.