Galanin reduces anoxic release of glutamate by an action on ATP sensitive K+ channels

Abstract

ATP sensitive K+ channels (K+ ATP) are a class of K+ channels that are inhibited by intracellular ATP (Noma, 1983; Stanfield, 1987). Initially discovered in the heart (Noma, 1983), they have now been described in several systems including skeletal muscle fibers, pancreatic B cells and more recently neurons (Stanfield, 1987; Aschcroft, 1988). In the pancreas they modulate insulin release; their blockade by glucose (following a rise in intracellular ATP) or directly by sulphonylureas — used for many years for the treatment of non-insulin dependent diabetes-produces a depolarization, the activation of voltage dependent Ca++ channels and release of insulin (Sturgess et al., 1985; Schmidt-Antomarchi et al., 1987). Their presence in neuron is important since these channels are highly suitable to modulate neuronal excitability according to metabolism (and ATP levels), and they may provide a target for drugs designed at antagonizing the deleterious effects of metabolic stress conditions such as anoxia or epilepsy. Since the hyperglycemic hormone galanin has been shown to activate K+ATP channels (De Weille et al., 1988) and is present in the hippocampal region (Melander et al., 1986; Ch’ng et al, 1985), I have examined its effects on the anoxic response of CA3 hippocampal neurons (Ben-Ari, 1990). I have also tested the effects of the potent sulphonylurea Glibenclamide which blocks K+ATP channels. The present observations are consistent with a modulatory action of galanin on anoxic release of transmitter.