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 pat
ch-clamp technique. Neurons were acutely dissociated from 21- to 30-day-old
mice. In the current-clamp mode, HCO3-/CO2 significantly hyperpolarized CA
1 neurons by more than 10 mV and decreased their input resistance. In addit
ion, the overall excitability of these neurons was lower in the presence of
HCO3-/CO2 than in HEPES. Spontaneous and evoked action potential firing fr
equency 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 tha
t the window currents were smaller in HCO3-/CO2 than in HEPES. Recovery fro
m 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 decrease
s the intrinsic excitability of CA1 neurons by altering not only the passiv
e properties of the neuronal membranes but also by changing several charact
eristics of the fast Na+ current, including activation and inactivation kin
etics as well as the recovery from inactivation and deactivation.