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 be primarily dependent upon influx of extracellular Ca²⁺, most of which is thought to cross nerve terminal membranes through N-type Ca²⁺ channels. Events in skeletal and cardiac muscle, in contrast, are regulated to a greater extent by intracellular Ca²⁺ exchange between cytosol and intracellular organelles such as sarcoplasmic reticulum. It is not known to what extent corresponding intracellular organelles, i.e. endoplasmic reticulum (ER), contribute to cytosolic Ca²⁺ transients and norepinephrine (NE) release from cardiac sympathetic nerves. Heart rate and NE release were measured in isolated perfused guinea pig hearts during 1-min stimulations (5 V, 4 Hz, 2 ms) of the right stellate ganglia prior to (S1), during the administration of (S2), and after (S3) the removal of ryanodine (1 μM) from the perfusate. Ryanodine is a selective modulator of caffeine-sensitive Ca²⁺ stores in ER. Baseline heart rates decreased significantly in the presence of ryanodine, documenting its physiological effects on cardiac cells. However, there was no detectable effect of ryanodine on nerve-stimulated increase in heart rate or NE release. These results indicate that the ryanodine-sensitive intracellular Ca²⁺ stores do not play a major role in cardiac sympathetic neurotransmission.