Deletion of the L-type calcium channel Ca V 1.3 but not Ca V 1.2 results in a diminished sAHP in mouse CA1 pyramidal neurons

Trains of action potentials in CA1 pyramidal neurons are followed by a prolonged calcium-dependent postburst afterhyperpolarization (AHP) that serves to limit further firing to a sustained depolarizing input. A reduction in the AHP accompanies acquisition of several types of learning and increases in the AHP are correlated with age-related cognitive impairment. The AHP develops primarily as the result of activation of outward calcium-activated potassium currents; however, the precise source of calcium for activation of the AHP remains unclear. There is substantial experimental evidence suggesting that calcium influx via voltage-gated L-type calcium channels (L-VGCCs) contributes to the generation of the AHP. Two L-VGCC subtypes are predominately expressed in the hippocampus, Ca V 1.2 and Ca V 1.3; however, it is not known which L-VGCC subtype is involved in generation of the AHP. This ambiguity is due in large part to the fact that at present there are no subunit-specific agonists or antagonists. Therefore, using mice in which the gene encoding Ca V 1.2 or Ca V 1.3 was deleted, we sought to determine the impact of alterations in levels of these two L-VCGG subtypes on neuronal excitability. No differences in any AHP measure were seen between neurons from Ca V 1.2 knockout mice and controls. However, the total area of the AHP was significantly smaller in neurons from Ca V 1.3 knockout mice as compared with neurons from wild-type controls. A significant reduction in the amplitude of the AHP was also seen at the 1 s time point in neurons from Ca V 1.3 knockout mice as compared with those from controls. Reductions in both the area and 1 s amplitude suggest the involvement of calcium influx via Ca V 1.3 in the slow AHP (sAHP). Thus, the results of our study demonstrate that deletion of Ca V 1.3, but not Ca V 1.2, significantly impacts the generation of the sAHP. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79416/1/20728_ftp.pd