title: Benzolamide, acetazolamide, and signal transduction in avian intrapulmonary chemoreceptors.
abstract: Intrapulmonary chemoreceptors (IPC) are CO(2)-sensitive sensory neurons that innervate the lungs of birds, help control the rate and depth of breathing, and require carbonic anhydrase (CA) for normal function. We tested whether the CA enzyme is located intracellularly or extracellularly in IPC by comparing the effect of a CA inhibitor that is membrane permeable (iv acetazolamide) with one that is relatively membrane impermeable (iv benzolamide). Single cell extracellular recordings were made from vagal filaments in 16 anesthetized, unidirectionally ventilated mallards (Anas platyrhynchos). Without CA inhibition, action potential discharge rate was inversely proportional to inspired PCO(2) (-9.0 +/- 0.8 s(-1). lnTorr(-1); means +/- SE, n = 16) and exhibited phasic responses to rapid PCO(2) changes. Benzolamide (25 mg/kg iv) raised the discharge rate but did not alter tonic IPC PCO(2) response (-9.8 +/- 1.6 s(-1). lnTorr(-1), n = 8), and it modestly attenuated phasic responses. Acetazolamide (10 mg/kg iv) raised IPC discharge, significantly reduced tonic IPC PCO(2) response to -3.5 +/- 3.6 s(-1). lnTorr(-1) (n = 6), and severely attenuated phasic responses. Results were consistent with an intracellular site for CA that is less accessible to benzolamide. A model of IPC CO(2) transduction is proposed.
authors.affiliation: Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona 86011-5640, USA. steven.hempleman@nau.edu
authors.forename: S C
authors.initials: SC
authors.lastname: Hempleman
authors.forename: T A
authors.initials: TA
authors.lastname: Rodriguez
authors.forename: Y A
authors.initials: YA
authors.lastname: Bhagat
authors.forename: R S
authors.initials: RS
authors.lastname: Begay
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001574:Benzolamide / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000494:pharmacology / Q000502:physiology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D004372:Ducks; D005260:Female; D001239:Inhalation; D008168:Lung / Q000294:innervation*; D008297:Male; D008954:Models, Biological; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010313:Partial Pressure; D011956:Receptors, Cell Surface; D012044:Regression Analysis; D015398:Signal Transduction / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D011956:Receptors, Cell Surface; D002245:Carbon Dioxide; D001574:Benzolamide; D000086:Acetazolamide