Contribution of Ca2+-activated K+ channels to central chemosensitivity in cultivated neurons of fetal rat medulla.
Neurons in fetal rat medullary slices that exhibited spontaneous electrical activity after blockade of synaptic transmission were investigated for their response to decreases in extracellular pH. Increases in [H+] (induced either by fixed acid or increases in PCO2) induced a significant increase in the frequency of action potentials, associated with a membrane depolarization, and/or increases in the slope of the interspike depolarization. In addition, CO2/H+ prolonged the repolarizing phase of action potentials and reduced the afterhyperpolarization, suggesting that K+ channels were the primary site of CO2/H+ action. The type of K+ channel that was modulated by CO2/H+ was identified by application of agents that inhibited Ca2+-activated K+ channels either directly (tetraethylammonium chloride, TEA) or indirectly (Cd2+ ions) by inhibiting Ca2+ influx. CO2/H+ effects on neuronal activity were abolished after application of these blockers. The contribution of Ca2+-activated K+ channels to H+ sensitivity of these neurons was confirmed further in voltage-clamp experiments in which outward rectifying I-V curves were recorded that revealed a zero current potential of -70 mV. CO2/H+ induced a prominent reduction in outward currents and shifted the zero current potential to more positive membrane potentials (mean -63 mV). The CO2/H+-sensitive current reversed at -72 mV and was blocked by external application of TEA. It is concluded that CO2/H+ exerts its stimulatory effects on fetal medullary neurons by inhibition of Ca2+-activated K+ channels, either directly or indirectly, by blocking voltage-dependent Ca2+ channels, which in turn results in a reduction of K+ efflux and in cell depolarization.
Wellner-Kienitz
M C
MC
Institut für Physiologie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
Shams
H
H
Scheid
P
P
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002245:Carbon Dioxide / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005333:Fetus / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008526:Medulla Oblongata / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D019789:Tetraethylammonium / Q000494:pharmacology
D015221:Potassium Channels; D002245:Carbon Dioxide; D019789:Tetraethylammonium; D002118:Calcium