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(a) Schematic illustrating the topography of the high voltage-activated calcium channel complex showing the main pore-forming α₁ subunit and ancillary subunits. The α₁ and δ subunits are integral membrane proteins, the β subunit is intracellular and binds directly to the α_1, while the α₂ subunit is thought to be largely extracellular. (b) Schematic diagram showing structure of the calcium channel α₁ subunit with its four domain structure. (c) The left panel shows the phylogenic relationship between the ten known calcium channel α₁ subunits. Ca_V1 subunits form the L-type subfamily, Ca_V2 channels the P/Q-type, N-type and R-type, and the Ca_V3 subunits form the low voltage-activated T-type calcium channels. The right panel shows representative traces of calcium currents recorded from reticular thalamic neurons in response to depolarization of the membrane potential. The upper trace shows a slow inactivating high voltage-activated current and the lower trace shows the fast inactivating low voltage-activated current.

Approximate positions of spontaneous loss of function mutations in tottering (tg) and it’s alleles (rolling, rocker, leaner, and tg 4J) are shown by black circles in pore forming alpha subunit (Cacna1a). Positions of two loss of function human mutations producing absence epilepsy, ataxia +/− episodic dyskinesia are shown with stars. Lethargic mutation interrupts interaction of cytoplasmic regulatory beta subunit (CacnB4) with the alpha subunit, and ducky results in defective membrane spanning a2delta subunit (Cacna2d2). Stargazer mutation shown in transmembrane gamma subunit (Cacng2) originally considered to be a member of the voltage-gated calcium channel as found in heteromeric muscle channels.

(A) Snapshot of calcium dye loaded slice (B) Change in fluorescence was measured for multiple cells and shown as a raster plot. Insert shows zoomed image of onset of synchronous network burst. The images were captured at 100 Hz by fast confocal microscopy equipped with EM-CCD camera (128×128 pixels). Note the stereotypic activation order for individual cells in multiple bursts.