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Concentration dependence of bicarbonate-induced calcium current modulation
C Bruehl1, W J Wadman, O W Witte
1Department of Neurology, Heinrich-Heine-University, 40225 Duesseldorf, Germany. bruehl@uni-duesseldorf.de
Journal of Neurophysiology
|November 9, 2000
Summary
Bicarbonate ions, not dissolved CO2, significantly reduce high-voltage-activated calcium currents in CA1 neurons. This finding is crucial for understanding central nervous system excitation during conditions like acidosis.
Area of Science:
- Neuroscience
- Electrophysiology
- Ion Channel Modulation
Background:
- High-voltage-activated calcium currents (HVA) in CA1 neurons are sensitive to buffer type.
- A switch from HEPES to CO2/HCO3- buffered solutions attenuates these currents.
Purpose of the Study:
- To determine whether bicarbonate ions or dissolved CO2 are responsible for the observed attenuation of HVA currents.
- To investigate the concentration-dependent effects of bicarbonate and CO2 on CA1 neuron currents.
Main Methods:
- Whole-cell patch-clamp technique on freshly isolated CA1 neurons.
- Application of solutions with varying concentrations of bicarbonate and CO2.
- Analysis of current amplitude, conductance, and voltage-dependence of activation/inactivation.
Main Results:
- Bicarbonate and CO2 caused a concentration-dependent decrease in maximal calcium conductance and peak current amplitude.
- The decrease followed the Hill equation, with a maximal attenuation of 69% and EC50 of 7.4 mM HCO3-.
- Hyperpolarizing shifts in activation and inactivation potentials were observed, with bicarbonate being the primary driver.
Conclusions:
- Bicarbonate ions, not dissolved CO2, modulate HVA currents in CA1 neurons.
- This modulation is concentration-dependent and affects current amplitude and voltage-dependence.
- Bicarbonate's role is significant for CNS excitation, especially in pathological states like hyperventilation and metabolic acidosis.