Voltage-gated calcium-selective channels

Ziconotide (45 Prialt ) Ziconotide (45) Peptide NP Animal Pain Acts as a selective /V-type voltage-gated calcium channel blocker 417 28... 

Verapamil (Isoptin, Covera), in addition to its use as an antiarrhythmic agent, has been employed extensively in the management of variant (Prinzmetal s) angina and effort-induced angina pectoris (see Chapters 17 and 19). It selectively inhibits the voltage-gated calcium channel that is vital for action potential genesis in slow-response myocytes, such as those found in the sinoatrial and A-V nodes. 

FIGURE 24.3 The 1,4-dihydropyridine nucleus as a privileged structure. In addition to classically established antagonist and activator interactions at the L-type of voltage-gated calcium channel appropriately substituted 1,4-dihydropyridines can interact, often with high selectivity, at a variety of other ion channels and receptors as depicted. 

Calcium channels have been shown to play a role in epilepsy as well [23]. Currently used antiepileptic drugs exhibit a wide spectrum of activity, including modulation of voltage-gated sodium and calcium channels. T-type calcium channels have been demonstrated to play an important role in absence epilepsy, a specific form of epilepsy characterized by brief lapses in consciousness correlated with spike-and-wave discharges in the electroencephalogram [14,24-28]. Ethosuximide 1 has been shown to block T-type calcium channels and is used clinically to treat absence epilepsy [25]. Several selective small-molecule T-type calcium channel antagonists have demonstrated efficacy in rodent epilepsy models (vide infra). 

The clinically available calcium chaimel antagonists have also proved to be invaluable as molecular probes with which to identify, isolate, and characterize calcium channels of the voltage-gated family. In particular, the 1,4-dihydropyridines with their high affinity, agonist-antagonist properties, and selectivity have become defined as molecular markers for the L-type chaimel. 

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