ziconotide and Neuroblastoma

Intracellular Ca(2+) ([Ca(2+)](i)) can rise primarily via release from intracellular storage sites (e.g., the endoplasmic reticulum) or via entry across the membrane down the steep concentration gradient. Ca(2+) can enter through two main classes of plasma membrane-located Ca(2+) channels: receptor operated and voltage sensitive. Voltage-sensitive Ca(2+) channels are involved in a wide and diverse array of physiological responses including neurotransmitter release. In addition, many guanine nucleotide protein (G) coupled receptors couple to voltage-sensitive Ca2(+) channels to reduce Ca(2+) influx.

Topics: Animals; Brain; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Cell Line; Cell Membrane; Female; Humans; Iodine Radioisotopes; Isradipine; Neuroblastoma; omega-Conotoxins; Rats; Rats, Wistar; Tritium

The actions of two omega-conopeptides on high-voltage-activated calcium channel currents in differentiated human neuroblastoma IMR32 cells were investigated. Similar to the previously reported action of omega-conopeptide GVIA, omega-conopeptide MVIIA irreversibly blocks IMR32 HVA calcium channel currents at low concentrations. Unlike GVIA action, however, novel omega-conopeptide SNX-260 (iodinated MVIIC) reversibly blocks these currents, also at low concentrations, with an IC50 near 50 nM. Different omega-conopeptides may be potent blockers of HVA calcium channel currents yet act either reversibly or irreversibly in a single cell.

Topics: Calcium Channel Blockers; Calcium Channels; Electric Conductivity; Humans; Intercellular Signaling Peptides and Proteins; Mollusk Venoms; Neuroblastoma; omega-Conotoxins; Peptides; Tumor Cells, Cultured