Effect of extracellular HCO3- on Na+ channel characteristics in hippocampal CA1 neurons

The effect of HCO3-/CO2 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, HCO3-/CO2 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 HCO3-/CO2 than in HEPES. Spontaneous and evoked action potential firing frequency was lower in the presence of HCO3-/CO2 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 HCO3-/CO2 than in HEPES. Recovery from inactivation and deactivation from the open state of the fast Na+ current was slower in HCO3-/CO2 than in HEPES. We conclude that HCO3-/CO2 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.