Brain calcium channels

Imbrici P, Jaffe SL, Eunson LH, Davies NP, Herd C, Robertson R, Kullmann DM, Hanna MG (2004) Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain... 

Westenbroek RE, Sakurai T, Elliott EM, Hell JW, Starr TV, Snutch TP, Catterall WA (1995) Immunochemical identification and subcellular distribution of the alpha 1A subunits of brain calcium channels. J Neurosci 15 6403-18... 

Carmignoto G, Pasti L, Pozzan T (1998) On the role of voltage-dependent calcium channels in calcium signaling of astrocytes in situ. J Neurosci 18 4637-4645 Cartier L, Hartley O, Dubois-Dauphin M, Krause KH (2005) Chemokine receptors in the central nervous system role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48 16 2... 

Veng LM, Mesches MH and Browning MD (2003). Age-related working memory impairment is correlated with increases in the L-type calcium channel protein alD (Cavl.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment. Molecular Brain Research, 110, 193-202. 

The two most frequently studied compounds with T-type calcium channel antagonist properties are ethosuximide 1 and mibefradil 3. However, the modest potency of ethosuximide ( 200 pM) [48] and the poor selectivity of mibefradil [49] make these compounds suboptimal tools for the investigation of these channels. Guided by a pharmacophore model [50], several analogs of 3 were prepared. Compound 4 represents the most potent compound identified (IC50 8 nM, patch-clamp assay) with good selectivity over the L-type calcium channel [51], Compound 4 showed a modest brain-to-plasma ratio (0.25) after oral dosing to rats at 50 mg/kg. However, no in vivo efficacy assay results have been reported with this compound. 

Symington SB, Clark JM (2005) Action of deltamethrin on N-type (Cav2.2) voltage-sensitive calcium channels in rat brain. Pestic Biochem Physiol 82 1-15... 

At the cellular level, chlordecone causes spontaneous neurotransmitter release (End et al. 1981) and increases in free intracellular calcium in synaptosomes (Bondy and Halsall 1988 Bondy and McKee 1990 Bondy et al. 1989 Komulainen and Bondy 1987). This appears to be due at least in part to increased permeability of the plasma membrane (Bondy and Halsall 1988 Bondy and McKee 1990 Bondy et al. 1989 Komulainen and Bondy 1987), activation of voltage-dependent calcium channels (Komulainen and Bondy 1987), and inhibition of brain mitochondrial calcium uptake (End et al. 1979, 1981). 

Studies using calcium channel blockers in the treatment of BPAD began in the late 1970s and early 1980s when it was suspected that abnormalities of calcium activity inside nerve cells might contribute to the brain dysfunction of BPAD. Unfortunately, all of the double-blind placebo controlled studies of calcium channel blockers in the treatment of BPAD have failed to demonstrate their efficacy. 

Reuter H (1996) Diversity and function of presynaptic calcium channels in the brain. Curr Op Neurobiol 6 331-337... 

Reynolds, I.J., Snowman, A.M. and Snyder, S.H. (1986) (-)-[3H] desmethoxyverapamil labels multiple calcium channel modulator receptors in brain and skeletal muscle membranes differentiation by temperature and dihydropyridines. The Journal of Pharmacology and Experimental Therapeutics, 237, 731—738. 

Bertrand S et al. The anticonvulsant, antihyperalgesic agent gabapentin is an agonist at brain gamma-aminobutyric acid type B receptors negatively coupled to voltage-dependent calcium channels. J Pharmacol Exper Therap 2001 298 15-24. 

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