title: Norepinephrine release from guinea pig cardiac sympathetic nerves is insensitive to ryanodine under physiological conditions.
abstract: 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.
authors.affiliation: University of Iowa College of Medicine, Iowa City 52242.
authors.forename: C A
authors.initials: CA
authors.lastname: Gurnett
authors.forename: C A
authors.initials: CA
authors.lastname: Whiteis
authors.forename: B J
authors.initials: BJ
authors.lastname: Pardini
authors.forename: P G
authors.initials: PG
authors.lastname: Schmid
mesh_terms: 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*
chemical_list: D012433:Ryanodine; D009638:Norepinephrine