Effect of Na+ and K+ channel blockade on baseline and anoxia-induced catecholamine release from rat carotid body.
Ionic membrane currents are hypothesized to play a major role in determining secretion from carotid body glomus cells, and increased secretion likely mediates the increase in nerve activity in response to hypoxia. The hypothesis that Na+ and K+ channels play an important role in determining secretion and nerve activity was tested by measuring single-fiber afferent nerve activity along with an estimate of free tissue catecholamine using Nafion-covered carbon-fiber micro-electrodes placed in rat carotid bodies in vitro. Baseline and anoxia-stimulated (1 min duration; PO2 of approximately 0 Torr at nadir) levels were quantified. Sham treatment had no significant effect. Tetrodotoxin (2 microns) ablated the nerve activity and reduced peak catecholamine (19.5 +/- 3.1 to 14.5 +/- 3.4 microM; P < 0.05). Cesium (10 microns) had no effect on catecholamine but reduced the nerve response (19.8 +/- 2.7 to 7.8 +/- 2.0 Hz; P < 0.05). 4-Aminopyridine (4 mM) significantly reduced the nerve response (17.2 +/- 3.7 to 4.9 +/- 1.9 Hz; P < 0.05) and increased the baseline (0.9 +/- 0.2 to 3.1 +/- 0.8 microM; P < 0.05) and reduced the peak catecholamine (10.0 to 4.3 +/- 0.8 microM; P < 0.05) levels. These results demonstrate that Na+ and K+ channels play an important role in modulating the secretory and nerve responses. However, channel blockers do not emulate severe hypoxia, suggesting that hypoxia transduction procedes, at least in part, through an alternate pathway.
Doyle
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Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Donnelly
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D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002395:Catecholamines / Q000378:metabolism*; D002586:Cesium / Q000494:pharmacology; D004594:Electrophysiology; D000860:Hypoxia / Q000378:metabolism*; D026902:Potassium Channel Blockers; D051381:Rats; D012016:Reference Values; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000494:pharmacology
D002395:Catecholamines; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D002586:Cesium; D013779:Tetrodotoxin; D015761:4-Aminopyridine