Changes in voltage-dependent calcium channel alpha1-subunit mRNA levels in the kindling model of epileptogenesis

The establishment of a focus of epileptiform activity in the hippocampus of the rat, using the kindling paradigm, leads to enhanced voltage-dependent calcium conductance of CA1 pyramidal neurones (G.C. Faas, M. Vreugdenhil, W.J. Wadman, Calcium currents in pyramidal CA1 neurones in vitro after kindling epileptogenesis in the hippocampus of the rat, Neuroscience 75 (1996) 57-67; M. Vreugdenhil, W.J. Wadman, Kindling-induced long-lasting enhancement of calcium in hippocampal CA1 area of the rat: relation to calcium-dependent inactivation, Neuroscience 59 (1994) 105-114). Using semi-quantitative in situ hybridization techniques, we investigated whether these changes were associated with an altered expression of the genes that encode for the alpha1A-E-subunits of the voltage-dependent calcium channels (VDCC). Kindling epileptogenesis was induced in rats that received an electrical tetanic stimulation of the Schaffer collateral/commissural fibre pathway in the hippocampus twice daily. Two groups of rats were studied before the appearance of generalized seizures, one group after at least 5 generalized seizures (fully kindled) and one group was investigated at long-term (28 days) after the last seizure. During the initial stages of epileptogenesis, the alpha1A-, alpha1D- and alpha1E-subunit mRNA levels were significantly increased in the different hippocampal subareas in comparison to the levels in control animals. In contrast, alpha1B-subunit gene expression decreased in the CA area and dentate gyrus. No significant change was observed in the alpha1C-I and alpha1C-II expression. At the fully kindled stage, the only significant change was an up-regulation of the alpha1B-subunit mRNA levels in the CA3 area, 24 h after the last seizure. No change in VDCC alpha1-subunit gene expression was found in animals investigated long-term after the establishment of the fully kindled state. Thus, the VDCC alpha1-subunit gene expression is altered in a subclass-specific manner during the early stages of kindling and may play a role in the establishment of a kindled focus, possibly caused by an alteration of the population of VDCCs involved in neurotransmitter release. The absence of long-lasting changes suggests that the maintenance of a kindled focus is not due to persisting alterations in VDCC alpha1 mRNA levels.