title: Contribution of Ca2+-activated K+ channels to central chemosensitivity in cultivated neurons of fetal rat medulla.
abstract: 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.
authors.affiliation: Institut für Physiologie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Wellner-Kienitz
authors.forename: H
authors.initials: H
authors.lastname: Shams
authors.forename: P
authors.initials: P
authors.lastname: Scheid
mesh_terms: 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
chemical_list: D015221:Potassium Channels; D002245:Carbon Dioxide; D019789:Tetraethylammonium; D002118:Calcium