CO2 chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing

Elevated levels of carbon dioxide increase lung ventilation in Helix aspersa. The hypercapnic response originates from a discrete respiratory chemosensory region in the dorsal subesophageal ganglia that contains CO(2)-sensitive neurons. We tested the hypothesis that pH-dependent inhibition of potassium channels in neurons in this region mediated the chemosensory response to CO(2). Cells isolated from the dorsal subesophageal ganglia retained CO(2) chemosensitivity and exhibited membrane depolarization and/or an increase in input resistance during an acid challenge. Isolated somata expressed two voltage-dependent potassium channels, an A-type and a delayed-rectifier-type channel (I(KA) and I(KDR)). Both conductances were inhibited during hypercapnia. The pattern of voltage dependence indicated that I(KA) was affected by extracellular or intracellular pH, but the activity of I(KDR) was modulated by extracellular pH only. Application of inhibitors of either channel mimicked many of the effects of acidification in isolated cells and neurons in situ. We also detected evidence of a pH-sensitive calcium-activated potassium channel (I(KCa)) in neurons in situ. The results of these studies support the hypothesis that I(KA) initiates the chemosensory response, and I(KDR) and I(KCa) prolong the period of activation of CO(2)-sensitive neurons. Thus multiple potassium channels are inhibited by acidosis, and the combined effect of pH-dependent inhibition of these channels enhances neuronal excitability and mediates CO(2) chemosensory responses in H. aspersa. We did not find a single "chemosensory channel," and the chemosensitive channels that we did find were not unique in any way that we could detect. The protein "machinery" of CO(2) chemosensitivity is probably widespread among neurons, and the selection process whereby a neuron acts or does not act as a respiratory CO(2) chemosensor probably depends on the resting membrane potential and synaptic connectivity.