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CaV3 T-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons


Dr Ray W. Turner, as above.


Spike output in many neuronal cell types is affected by low-voltage-activated T-type calcium currents arising from the Cav3.1, Cav3.2 and Cav3.3 channel subtypes and their splice isoforms. The contributions of T-type current to cell output is often proposed to reflect a differential distribution of channels to somatic and dendritic compartments, but the subcellular distribution of the various rat T-type channel isoforms has not been fully determined. We used subtype-specific Cav3 polyclonal antibodies to determine their distribution in key regions of adult Sprague–Dawley rat brain thought to exhibit T-type channel expression, and in particular, dendritic low-voltage-activated responses. We found a selective subcellular distribution of Cav3 channel proteins in cell types of the neocortex and hippocampus, thalamus, and cerebellar input and output neurons. In general, the Cav3.1 T-type channel immunolabel is prominent in the soma/proximal dendritic region and Cav3.2 immunolabel in the soma and proximal-mid dendrites. Cav3.3 channels are distinct in distributing to the soma and over extended lengths of the dendritic arbor of particular cell types. Cav3 distribution overlaps with cell types previously established to exhibit rebound burst discharge as well as those not recognized for this activity. Additional immunolabel in the region of the nucleus in particular cell types was verified as corresponding to Cav3 antigen through analysis of isolated protein fractions. These results provide evidence that different Cav3 channel isoforms may contribute to low-voltage-activated calcium-dependent responses at the somatic and dendritic level, and the potential for T-type calcium channels to contribute to multiple aspects of neuronal activity.

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