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 microM) 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 effect 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.
Gurnett
C A
CA
University of Iowa College of Medicine, Iowa City 52242.
Whiteis
C A
CA
Pardini
B J
BJ
Schmid
P G
PG
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013233:Stellate Ganglion / Q000166:cytology / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*
D012433:Ryanodine; D009638:Norepinephrine