Cav distribution, toxin inhibitors and potential effects of inhibition
| Cav Isoform | Distribution | Selective Toxin Inhibitors | Effects/Side Effects of Inhibition | References |
|---|---|---|---|---|
| Cav1.1–1.4 (L-type) (CACNA1S or C or D or F) | Skeletal muscle (1.1), (T-tubules), Cardiac muscle (1.2–1.3), smooth muscle (1.2), CNS (1.1–1.3), DRG (1.2–1.4), retina (1.4) lymphocytes (1.2–1.4), GIT (1.2), cochlea (1.3). | None known (dihydropyridines) | Widespread effects on cardiovascular system, 1.2 implicated in neuropathic pain in spinal cord. | Kim et al., 2001; Catterall et al., 2005b, 2007; Fossat et al., 2010 |
| Cav2.1 (P/Q type) (CACNA1A) splice variants | Brain, spinal cord, sympathetic neurons, DRG, endocrine cells, contribution to presynaptic neurotransmitter release at CNS, PNS, and neuromuscular junction. | ω-Conotoxins MVIIC ∼ MVIID > CVIB > CVIC ≫ MVIIA > GVIA ≫ CVID | Mutations in several neurological disorders, blockers produce partial inhibition of synaptic transmission. Peripheral side effects expected from autonomic and neuromuscular block. | Bourinet et al., 1999; Nudler et al., 2003; Catterall et al., 2005b, 2007 (For selectivity see Table 4.) |
| Spider toxins: ω-agatoxin IVA | ||||
| Cav2.2 (CACNA1B) splice variants | Brain, spinal cord, sympathetic neurons, DRG, contribution to presynaptic neurotransmitter release in CNS and PNS. | ω-Conotoxins CVIE = CVID = GVIA ≫ CVIA ∼ MVIIA > CVIB ∼ CVIC | Blockers produce inhibition of synaptic transmission throughout the nervous system. | Catterall et al., 2005b, 2007 (For selectivity see Table 4.) |
| Cav2.3 (CACNA1E) splice variants | Brain, spinal cord, sympathetic neurons, DRG, minor role in presynaptic neurotransmitter release in CNS and PNS, synaptic plasticity. | No conotoxins | Blockers modulate synaptic plasticity at some brain synapses. | Murakami et al., 2004; Catterall et al., 2005b, 2007; Matthews et al., 2007 (For selectivity see Table 4.) |
| Spider: SNX-482 | ||||
| Cav3.1 (CACNA1G) | Brain neurons localized to soma and dendrites. High expression in cerebellum and thalamus. Modulates action potential firing. Ovary, placenta, heart. | No conotoxins (pimozide, mibefradil, TTA-P2) | Small-molecule modulators may be useful for some CNS neurological disorders. | Catterall et al., 2005b, 2007; Yaksh, 2006; Triggle, 2007; Zamponi et al., 2009 |
| Cav3.2 (CACNA1H) | CNS, DRG neurons: localized to soma and dendrites. Modulates action potential firing. Also heart, liver, kidney, lung, skeletal muscle, pancreas. | No conotoxins | Pain modulation. Relaxation of coronary arteries, potential side effects from actions in other tissues. | Catterall et al., 2005b, 2007; Yaksh, 2006; Triggle, 2007; Zamponi et al., 2009; Choe et al., 2011 |
| Scorpion: kurtoxin (pimozide, mibefradil, Z123212,a TTA-P2) | ||||
| Cav3.3 (CACNA1I) | CNS neurons: localized to soma and dendrites. Modulates action potential firing. | No conotoxins (pimozide, TTA-P2, mibefradil very weak) | Presumably many side effects. | Catterall et al., 2005b, 2007; Yaksh, 2006; Triggle, 2007; Zamponi et al., 2009 |
↵a Z123212 (Hildebrand et al., 2011) also targets sodium channels.
PNS, peripheral nervous system; TTA-P2, 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide.