Effects of GABA on spontaneous [Ca]c dynamics and electrical properties of rat adrenal chromaffin cells

A large fraction of rat adrenal chromaffin cells (about 60%) shows spontaneous Ca²⁺]_c oscillations and spontaneous action potentials. In the present study the effects of γ-aminobutyric acid (GABA) on the spontaneous Ca²⁺]_c oscillations and electrical properties of rat adrenal chromaffin cells were investigated using Fura-2 Ca²⁺]_c imaging and patch clamp techniques. GABA inhibited the spontaneous Ca²⁺]_c oscillations in a reversible manner. The effect of GABA was mimicked by the GABA_A and GABA_C receptor agonist, muscimol, but not by the GABA_B receptor agonist, baclofen. Moreover, the effect was antagonized by the selective GABA_A receptor antagonist, bicuculline. The mode of the inhibition was all-or-none, and the threshold concentration at which the inhibition occurred varied widely (50 μM to over 1 μM) from cell to cell. GABA (100 μM) elicited a transient burst of action potentials of diminished amplitude, which was followed by arrest of action potentials. Further analysis showed that GABA (100 μM) induced inward whole-cell currents in voltage-clamp experiments and produced depolarization and membrane conductance increase in current-clamp experiments. The effects appear to be due to an increase in chloride ion conductance since the degree of GABA-induced depolarization depended on the pipette Cl⁻]. These results suggest that GABA, acting through GABA_A receptor, may play a role in the physiological regulation of rat adrenal chromaffin cells by directly modifying the discharge of spontaneous action potentials and spontaneous Ca²⁺]_c oscillations.