Structure, function and therapeutic potential of omega conopeptides: novel blockers of neuronal calcium channels

Abstract

Recent molecular cloning strategies have revealed that the diversity of voltage-sensitive calcium channels (VSCC) in the nervous system is much larger than indicated by electrophysiological studies. Elucidation of the physiological functions of these novel classes of VSCC requires pharmacological tools such as the blockers which were highly useful in characterizing the L-type VSCC in skeletal, smooth and cardiac muscle. Omega conopeptides found in the venom of fish-eating marine snails are proving to be highly selective blockers of neuronal VSCC. Several omega conopeptides have been isolated from a variety ofConus, characterized and synthesized. Biochemical, electrophysiological and morphological studies with these synthetic conopeptides have shown that novel types of VSCC are located in discrete regions of the brain and control the release of neurotransmitters in a highly selective manner, hitherto unsuspected. Pharmacological studies in animal models of cerebral ischemia have shown that omega conopeptides which selectively block N-type VSCC are highly effective in preventing brain damage caused by the loss of oxygen supply to the brain during the ischemia episode.