Concentration dependence of bicarbonate-induced calcium current modulation

High-voltage-activated calcium currents (HVA) of CA1 neurons are prominentl y attenuated following a switch from HEPES-buffered solution to one buffere d with CO2/HCO3-. In the present study we investigated whether bicarbonate ions or the dissolved CO2 induce this alteration in current characteristic. The study was carried out on freshly isolated CA1 neurons using the whole cell patch-clamp technique. Maximal calcium conductance and the mean peak a mplitude of the currents showed a concentration-dependent decrease when cel ls were consecutively bathed in solutions containing increasing amounts of bicarbonate and CO2. This decrease is best described by the Hill equation, yielding a maximal attenuation of 69%, a half-maximal concentration (EC50) of 7.4 mM HCO3-, and a Hill coefficient of 1.8. In parallel, the potentials of half-maximal activation (V-h,V-a) and inactivation (V-h,V-i) were linea rly shifted in hyperpolarizing direction with a maximal shift, in the 10% C O2/37 mM HCO3- containing solution of 10 +/- 1 mV for V-h,V-a (n = 23) and 17 +/- 1.4 mV for V-h,V-i (n = 18). When currents were evoked in solutions containing equal concentrations of bicarbonate but different amounts of CO2 , only nonsignificant changes were observed, while marked alterations of th e currents were induced when bicarbonate was changed and CO2 held stable. T he experiments suggest that bicarbonate is the modulating agent and not CO2 . This bicarbonate-induced modulation may be of critical relevance for the excitation level of the CNS under pathological situation with altered conce ntration of this ion, such as hyperventilation and metabolic acidosis.