Benzolamide, acetazolamide, and signal transduction in avian intrapulmonary chemoreceptors

Intrapulmonary chemoreceptors (IPC) are CO2-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 comp aring the effect of a CA inhibitor that is membrane permeable (iv acetazola mide) with one that is relatively membrane impermeable (iv benzolamide). Si ngle cell extracellular recordings were made from vagal filaments in 16 ane sthetized, unidirectionally ventilated mallards (Anas platyrhynchos). Witho ut CA inhibition, action potential discharge rate was inversely proportiona l to inspired PCO2 (-9.0 +/- 0.8 s(-1).lnTorr(-1); means +/- SE, n = 16) an d exhibited phasic responses to rapid PCO2 changes. Benzolamide (25 mg/kg i v) raised the discharge rate but did not alter tonic IPC PCO2 response (-9. 8 +/- 1.6 s(-1).lnTorr(-1), n = 8), and it modestly attenuated phasic respo nses. Acetazolamide (10 mg/kg iv) raised IPC discharge, significantly reduc ed tonic IPC PCO2 response to -3.5 +/- 3.6 s(-1).lnTorr(-1) (n = 6), and se verely attenuated phasic responses. Results were consistent with an intrace llular site for CA that is less accessible to benzolamide. A model of IPC C O2 transduction is proposed.