A computational analysis of central CO2 chemosensitivity in Helix aspersa.
We created a single-compartment computer model of a CO(2) chemosensory neuron using differential equations adapted from the Hodgkin-Huxley model and measurements of currents in CO(2) chemosensory neurons from Helix aspersa. We incorporated into the model two inward currents, a sodium current and a calcium current, three outward potassium currents, an A-type current (I(KA)), a delayed rectifier current (I(KDR)), a calcium-activated potassium current (I(KCa)), and a proton conductance found in invertebrate cells. All of the potassium channels were inhibited by reduced pH. We also included the pH regulatory process to mimic the effect of the sodium-hydrogen exchanger (NHE) described in these cells during hypercapnic stimulation. The model displayed chemosensory behavior (increased spike frequency during acid stimulation), and all three potassium channels participated in the chemosensory response and shaped the temporal characteristics of the response to acid stimulation. pH-dependent inhibition of I(KA) initiated the response to CO(2), but hypercapnic inhibition of I(KDR) and I(KCa) affected the duration of the excitatory response to hypercapnia. The presence or absence of NHE activity altered the chemosensory response over time and demonstrated the inadvisability of effective intracellular pH (pH(i)) regulation in cells designed to act as chemostats for acid-base regulation. The results of the model indicate that multiple channels contribute to CO(2) chemosensitivity, but the primary sensor is probably I(KA). pH(i) may be a sufficient chemosensory stimulus, but it may not be a necessary stimulus: either pH(i) or extracellular pH can be an effective stimuli if chemosensory neurons express appropriate pH-sensitive channels. The lack of pH(i) regulation is a key feature determining the neuronal activity of chemosensory cells over time, and the balanced lack of pH(i) regulation during hypercapnia probably depends on intracellular activation of pH(i) regulation but extracellular inhibition of pH(i) regulation. These general principles are applicable to all CO(2) chemosensory cells in vertebrate and invertebrate neurons.
Chernov
Mykyta M
MM
Department of Physiology, 1 Medical Center Drive, Dartmouth Medical School, Lebanon, NH 03756-0001, USA.
Daubenspeck
J Andrew
JA
Denton
Jerod S
JS
Pfeiffer
Jason R
JR
Putnam
Robert W
RW
Leiter
J C
JC
D000136:Acid-Base Equilibrium / Q000502:physiology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000502:physiology*; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors; D004594:Electrophysiology; D045604:Extracellular Fluid / Q000378:metabolism; D006372:Helix, Snails / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism; D008959:Models, Neurological; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors; D011522:Protons; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013997:Time Factors
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; D002245:Carbon Dioxide