Effect of extracellular HCO(3)(-) on Na(+) channel characteristics in hippocampal CA1 neurons.
The effect of HCO(3)(-)/CO(2) on membrane properties of isolated hippocampal CA1 neurons was studied with the use of the whole cell configuration of the patch-clamp technique. Neurons were acutely dissociated from 21- to 30-day-old mice. In the current-clamp mode, HCO(3)(-)/CO(2) significantly hyperpolarized CA1 neurons by more than 10 mV and decreased their input resistance. In addition, the overall excitability of these neurons was lower in the presence of HCO(3)(-)/CO(2) than in HEPES. Spontaneous and evoked action potential firing frequency was lower in the presence of HCO(3)(-)/CO(2) than in its absence. In the voltage-clamp mode, both activation and steady-state inactivation of a fast Na(+) current were shifted in the hyperpolarized direction in such a way that the window currents were smaller in HCO(3)(-)/CO(2) than in HEPES. Recovery from inactivation and deactivation from the open state of the fast Na(+) current was slower in HCO(3)(-)/CO(2) than in HEPES. We conclude that HCO(3)(-)/CO(2) decreases the intrinsic excitability of CA1 neurons by altering not only the passive properties of the neuronal membranes but also by changing several characteristics of the fast Na(+) current, including activation and inactivation kinetics as well as the recovery from inactivation and deactivation.
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Department of Pediatrics (Section of Respiratory Medicine), Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Yao
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Haddad
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D001639:Bicarbonates; D015222:Sodium Channels; D002245:Carbon Dioxide; D013779:Tetrodotoxin; D012964:Sodium