Adenosine and ATP link PCO2 to cortical excitability via pH.
In addition to affecting respiration and vascular tone, deviations from normal CO(2) alter pH, consciousness, and seizure propensity. Outside the brainstem, however, the mechanisms by which CO(2) levels modify neuronal function are unknown. In the hippocampal slice preparation, increasing CO(2), and thus decreasing pH, increased the extracellular concentration of the endogenous neuromodulator adenosine and inhibited excitatory synaptic transmission. These effects involve adenosine A(1) and ATP receptors and depend on decreased extracellular pH. In contrast, decreasing CO(2) levels reduced extracellular adenosine concentration and increased neuronal excitability via adenosine A(1) receptors, ATP receptors, and ecto-ATPase. Based on these studies, we propose that CO(2)-induced changes in neuronal function arise from a pH-dependent modulation of adenosine and ATP levels. These findings demonstrate a mechanism for the bidirectional effects of CO(2) on neuronal excitability in the forebrain.
Dulla
Chris G
CG
Neuroscience Program, Department of Neurology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Dobelis
Peter
P
Pearson
Tim
T
Frenguelli
Bruno G
BG
Staley
Kevin J
KJ
Masino
Susan A
SA
D000143:Acids / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D045604:Extracellular Fluid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D016857:Hypocapnia / Q000378:metabolism / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000143:Acids; D043682:Receptor, Adenosine A1; D018048:Receptors, Purinergic P2; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D000241:Adenosine