Calcium and avian intrapulmonary chemoreceptor response to CO₂

Intrapulmonary chemoreceptors (IPC) are highly responsive respiratory chemoreceptors that innervate the lungs of birds and diapsid reptiles. IPC are stimulated by low levels of lung PCO₂, inhibited by high levels of lung PCO₂, and their vagal afferents serve as a sensory limb for reflex adjustments of breathing depth and rate. Most IPC exhibit both phasic and tonic sensitivity to CO₂, and spike frequency adaptation (SFA) contributes to their phasic CO₂ responsiveness. To test whether CO₂ responsiveness and SFA in IPC is modulated by a Ca ²⁺-linked mechanism, we quantified the role of transmembrane Ca ²⁺ fluxes and Ca²⁺-related channels on single-unit IPC function in response to phasic changes in inspired PCO₂. We found that 1) broad-spectrum blockade of Ca²⁺ channels using cadmium or cobalt and blockade of L-type Ca²⁺ channels using nifedipine increased IPC discharge; 2) activation of L-type Ca²⁺ channels using BAY K 8644 reduced IPC discharge; 3) blockade of Ca²⁺-activated potassium channels using charybdotoxin (antagonist of large-conductance Ca ²⁺-dependent K⁺ channel) increased IPC discharge, but neither charybdotoxin nor apamin affected SFA; and 4) blockade of chloride channels, including Ca²⁺-activated chloride channels, with niflumic acid decreased IPC discharge at low PCO₂ and increased IPC discharge at high PCO₂, resulting in a net attenuation of the IPC CO ₂ response. We conclude that Ca²⁺ influx through L-type Ca²⁺ channels has an inhibitory effect on IPC afferent discharge and CO₂ sensitivity, that spike frequency adaptation is not due to apamin- or charybdotoxin-sensitive Ca²⁺-activated K⁺ channels in IPC, and that chloride channels blocked by niflumic acid help modulate IPC CO₂ responses.