ATP causes glomus cell [Ca2+]c increase without corresponding increases in CSN activity.
The hypothesis that an increase in intracellular calcium [Ca(2+)](c) in carotid body (CB) glomus cells will cause enhanced afferent carotid sinus nerve (CSN) activities was tested in the rat CB in-vitro with the use of extracellular ATP. ATP caused a dose dependent [Ca(2+)](c) increase in identified glomus cells. A major part of total [Ca(2+)](c) increase (2/3) was due to the [Ca(2+)] influx. The rest of [Ca(2+)](c) increase (1/3) was due to the release of [Ca(2+)] from the endoplasmic reticulum (ER) [Ca(2+)] stores, and it was inhibited by the pretreatment of cells with cyclopiazonic acid (CPA), an intracellular Ca(2+)-ATPase blocker. Suramin, a purinergic P(2) receptor membrane blocker, blocked [Ca(2+)] influx due to ATP in the presence of extracellular [Ca(2+)]. Perfusion with 5 and 10 microM ATP stimulated CSN activities in both normoxia (Nx) and hypoxia (Hx). Above that level, 100 microM ATP induced slight initial stimulation in CSN activities which were subsided subsequently in Nx and partly diminished in Hx, while 500 microM ATP completely inhibited CSN activities in Nx and Hx after a slight initial stimulation. Electrophysiological measurements of the glomus cell membrane potential in the presence of ATP (100 microM) during Nx indicated cellular enhanced outward K(+) current and hyperpolarization, suggesting potential mechanism for the inhibition of CSN activities. Thus, ATP dependent linear increases in [Ca(2+)](c) did not give rise to a corresponding increase in CSN activities, contravening the normally expected increase in CSN activities following [Ca(2+)](c) rise.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000344:Afferent Pathways; D000818:Animals; D001933:Brain Stem / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002344:Carotid Body / Q000166:cytology / Q000378:metabolism*; D002346:Carotid Sinus / Q000294:innervation* / Q000502:physiology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017950:Ganglia, Sensory / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D058914:Purinergic Antagonists; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D018377:Neurotransmitter Agents; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D013498:Suramin; D000255:Adenosine Triphosphate; D014446:Tyrosine 3-Monooxygenase; D011188:Potassium