NOREPINEPHRINE RELEASE FROM GUINEA-PIG CARDIAC SYMPATHETIC-NERVES IS INSENSITIVE TO RYANODINE UNDER PHYSIOLOGICAL CONDITIONS

The activation of neurotransmitter release in nerve cells appears to b e primarily dependent upon influx of extracellular Ca2+, most of which is thought to cross nerve terminal membranes through N-type Ca2+ chan nels. Events in skeletal and cardiac muscle, in contrast, are regulate d to a greater extent by intracellular Ca2+ exchange between cytosol a nd intracellular organelles such as sarcoplasmic reticulum. It is not known to what extent corresponding intracellular organelles, i.e. endo plasmic reticulum (ER), contribute to cytosolic Ca2+ transients and no repinephrine (NE) release from cardiac sympathetic nerves. Heart rate and NE release were measured in isolated perfused guinea pig hearts du ring 1-min stimulations (5 V, 4 Hz, 2 ms) of the right stellate gangli a prior to (S1), during the administration of (S2), and after (S3) the removal of ryanodine (1 muM) from the perfusate. Ryanodine is a selec tive modulator of caffeine-sensitive Ca2+ stores in ER. Baseline heart rates decreased significantly in the presence of ryanodine, documenti ng its physiological effect on cardiac cells. However, there was no de tectable effect of ryanodine on nerve-stimulated increase in heart rat e or NE release. These results indicate that the ryanodine-sensitive i ntracellular Ca2+ stores do not play a major role in cardiac sympathet ic neurotransmission.