Deletion of the L-type calcium channel CaV1.3 but not CaV1.2 results in a diminished sAHP in mouse CA1 pyramidal neurons
| Autor: | Geoffrey G. Murphy, Amy E. Gamelli, Brandon C. McKinney, Jessica A. White |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Mice 129 Strain Patch-Clamp Techniques Calcium Channels L-Type Cognitive Neuroscience Action Potentials chemistry.chemical_element Mice Transgenic In Vitro Techniques Calcium Article Cav1.2 Cav1.3 Mice Animals L-type calcium channel Calcium Signaling CA1 Region Hippocampal Calcium signaling Mice Knockout biology Voltage-dependent calcium channel Afterhyperpolarization Electrophysiological Phenomena Mice Inbred C57BL chemistry Knockout mouse biology.protein Female Neuroscience |
| Zdroj: | Hippocampus. 21:133-141 |
| ISSN: | 1050-9631 |
| DOI: | 10.1002/hipo.20728 |
| Popis: | Trains of action potentials in CA1 pyramidal neurons are followed by a prolonged calcium-dependent postburst afterhyperpolari- zation (AHP) that serves to limit further firing to a sustained depolariz- ing 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, CaV1.2 and CaV1.3; 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 CaV1.2 or CaV1.3 was deleted, we sought to determine the impact of alterations in levels of these two L-VCGG sub- types on neuronal excitability. No differences in any AHP measure were seen between neurons from CaV1.2 knockout mice and controls. How- ever, the total area of the AHP was significantly smaller in neurons from CaV1.3 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 CaV1.3 knockout mice as compared with those from controls. Reductions in both the area and 1 s amplitude suggest the involvement of calcium influx via CaV1.3 in the slow AHP (sAHP). Thus, the results of our study demonstrate that dele- tion of CaV1.3, but not CaV1.2, significantly impacts the generation of the sAHP. V C 2009 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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