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

Abstract

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.

Transient outwardly rectifying A currents are involved in the firing rate response to altered CO2 in chemosensitive locus coeruleus neurons from neonatal rats

“…Thus, in mammalian central chemosensitive neurons, the A current plays a role in chemosensitive signaling in LC neurons and likely in NTS neurons as well (31). Combined with previous work that showed a role for an A current in the response of chemosensitive neurons from the invertebrate Helix aspersa (12), our data suggest that the A current may play a widespread role in chemosensitive neurons from many different animals from various taxa.…”

“…A CURRENTS AND THE CHEMOSENSITIVE RESPONSE OF LC NEURONS signaling in mammalian neurons, although the A current has been shown to play a major role in the response of chemosensitive neurons from the snail, Helix aspersa (12).…”

“…However, common channels, like Kir channels (45), TASK channels (2), and KCa channels (62) have been implicated in central chemosensitive signaling in mammalian neurons. Further, the involvement of an A current and a delayed-rectifying K ϩ current in chemosensitivity in snail neurons has been shown (12). The fact that these channels are widely distributed but contribute to central chemosensitivity in select neurons suggests that these channels come in a variety of forms involving different subunits or splice variants with differing sensitivities to elevated CO 2 /H ϩ .…”

Carbon dioxide sensitivity and its role in multifunctional neurons in the mollusk Onchidium

“…This can be explained by a mechanism in which CO 2 first increases Cl − conductance, as it does in Aplysia (Brown and Berman, 1970;. After a delay, this increase is accompanied by a decrease in K + conductance, as seen in Helix (Denton et al, 2007). The differences in responses to CO 2 across preparations may be directly related to the different distributions of Cl − and K + channels.…”

“…Differences in the intracellular Cl − concentration in individual neurons generate both depolarizing and hyperpolarizing responses (Brown and Berman, 1970;. Using the terrestrial mollusk Helix, Denton et al (2007) reported that excitatory responses to CO 2 were caused by a decrease in several types of K + conductance, and that this effect derived from a production of H + . These former studies, however, did not consider the participation of a direct CO 2 effect on the neurons.…”