GABAB-mediated modulation of the voltage-gated Ca2+ channels

Abstract

1. The amino acid, gamma-aminobutyric acid (GABA), activates two different receptor types (Bowery et al., 1980; reviewed by Ogata, 1990a). 2. GABAA receptors are bicuculline-sensitive and are coupled to Cl- channels, while activation of bicuculline-insensitive GABAB receptors has been implicated in the modulation of Ca2+ (Dunlap and Fischbach, 1981) and K+ (Gahwiler and Brown, 1985; Inoue et al., 1985a,b; reviewed by Ogata, 1990b) channels. 3. Baclofen is a specific agonist for GABAB receptors (Bowery et al., 1980). In rat sensory neurones, baclofen suppresses the membrane Ca2+ current (ICa) by a mechanism involving a partussis toxin-sensitive G protein (Holz et al., 1986; Scott and Dolphin, 1986). 4. It has been shown that the inhibitory effect of baclofen is more potent on the early portion of ICa than on the later portion and consequently the rate of ICa activation is slowed (Deisz and Lux, 1985; Dolphin and Scott, 1986). 5. The mechanisms underlying these GABAB-mediated modulation of ICa is not fully understood. This article reviews the inhibitory action of baclofen on ICa in sensory neurones.