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.
- Intracellular pH
- Signal transduction
- Spike frequency adaptation
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
- Physical Therapy, Sports Therapy and Rehabilitation