The Journal of Neurophysiology Vol. 84 No. 5 November 2000, pp. 2277-2283
Copyright ©2000 by the American Physiological Society

Concentration Dependence of Bicarbonate-Induced Calcium Current Modulation

 ¹Department of Neurology, Heinrich-Heine-University, 40225 Duesseldorf, Germany; and  ²Institute for Neurobiology, University of Amsterdam, 1098 SM Amsterdam, The Netherlands

Bruehl, C., W. J. Wadman, and O. W. Witte. Concentration Dependence of Bicarbonate-Induced Calcium Current Modulation. J. Neurophysiol. 84: 2277-2283, 2000. High-voltage-activated calcium currents (HVA) of CA1 neurons are prominently attenuated following a switch from HEPES-buffered solution to one buffered 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 amplitude of the currents showed a concentration-dependent decrease when cells 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,a) and inactivation (V_h,i) were linearly shifted in hyperpolarizing direction with a maximal shift, in the 10% CO₂/37 mM HCO₃ containing solution of 10 ± 1 mV for V_h,a (n = 23) and 17 ± 1.4 mV for V_h,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 the currents were induced when bicarbonate was changed and CO₂ held stable. The 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 concentration of this ion, such as hyperventilation and metabolic acidosis.