Calcium and avian intrapulmonary chemoreceptor response to CO sub(2)

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 PCO sub(2), inhibited by high levels of lung PCO sub(2), 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 CO sub(2), and spike frequency adaptation (SFA) contributes to their phasic CO sub(2) responsiveness. To test whether CO sub(2) responsiveness and SFA in IPC is modulated by a Ca super(2+)-linked mechanism, we quantified the role of transmembrane Ca super(2+) fluxes and Ca super(2+)-related channels on single-unit IPC function in response to phasic changes in inspired PCO sub(2). We found that 1) broad-spectrum blockade of Ca super(2+) channels using cadmium or cobalt and blockade of L-type Ca super(2+) channels using nifedipine increased IPC discharge; 2) activation of L-type Ca super(2+) channels using BAY K 8644 reduced IPC discharge; 3) blockade of Ca super(2+)-activated potassium channels using charybdotoxin (antagonist of large-conductance Ca super(2+)-dependent K super(+) channel) increased IPC discharge, but neither charybdotoxin nor apamin affected SFA; and 4) blockade of chloride channels, including Ca super(2+)-activated chloride channels, with niflumic acid decreased IPC discharge at low PCO sub(2) and increased IPC discharge at high PCO sub(2), resulting in a net attenuation of the IPC CO sub(2) response. We conclude that Ca super(2+) influx through L-type Ca super(2+) channels has an inhibitory effect on IPC afferent discharge and CO sub(2) sensitivity, that spike frequency adaptation is not due to apamin- or charybdotoxin-sensitive Ca super(2+)-activated K super(+) channels in IPC, and that chloride channels blocked by niflumic acid help modulate IPC CO sub(2) responses.