gamma-Aminobutyric acid is a neuromodulator in sinus node of guinea pig heart.

A possible neurotransmitter role for gamma-aminobutyric acid (GABA) in the sinus node of guinea pig heart was examined. Among right atrium, left atrium, right ventricle, left ventricle, and sinus node, the highest amount of the endogenous GABA was found in the sinus node (1,240.6 +/- 120.8 nmol/g protein). The neuronal uptake of [3H]GABA was also the highest in the sinus node and kinetic analysis of the [3H]GABA uptake system in the sinus node showed one saturable component (Km = 17.3 microM, Vmax = 2.18 nmol.g protein-1.10 min-1). Autoradiography of [3H]GABA demonstrated heavy labeling of [3H]GABA in the nonmyelinated nerve fibers within the sinus node compared with findings in the atrial muscle. Electrical transmural stimulation evoked a Ca(2+)-dependent tetrodotoxin-sensitive release of [3H]GABA from the isolated sinus node preloaded with [3H]GABA in the presence of beta-alanine, thereby indicating that the [3H]GABA in the nerve is released from nerve terminals following electrical stimulation. These results provide evidence for the neuromodulator role of GABA in the sinus node of the guinea pig.