ω-agatoxin IVA blocks nicotinic receptor channels in bovine chromaffin cells

• Published in: FEBS letters 1995-03, Vol.362 (1), p.15-18
• Main Authors: Granja, Ricardo, Fernández-Fernández, JoséM, Izaguirre, Victor, González-García, Carmen, Ceña, Valentin
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Adrenal Medulla - drug effects; Adrenal Medulla - metabolism; Animals; Calcium channel; Calcium Channels - drug effects; Calcium Channels - metabolism; Canals de potassi; Cattle; Cells, Cultured; Chromaffin cell; Epinephrine - metabolism; Nicotina; Nicotine - pharmacology; Nicotinic receptor; Norepinephrine - metabolism; omega-Agatoxin IVA; P-type; Patch-Clamp Techniques; Potassium - pharmacology; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - metabolism; Secretion; Spider Venoms - pharmacology; ω-Agatoxin IVA
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)00149-4

We have studied the contribution of P-type voltage-dependent Ca 2+ channels to both catacholamine (CA) and ATP secretion from bovine chromaffin cells induced by high K + or nicotine using ω-agatoxin IVA, a selective blocker of P-type voltage-dependent Ca 2+ channels. We found that high K + (75 mM) induced the release of about 13% of norepinephrine, 5% epinephrine and 11% ATP, and that ω-agatoxin (100 nM) did not affect this secretion. However, both nicotine-induced CA and ATP secretion were significantly blocked (about 50%) by ω-agatoxin IVA (100 nM). In addition, this toxin also reversibly blocked (about 70%) the inward current induced by nicotine in bovine chromaffin cells. The results suggest that, besides its known action of blocking P-type voltage-dependent channels, ω-agatoxin is a potent and reversible blocker of the nicotinic receptor channel in chromaffin cells, and that this action would explain the blockade of nicotine-induced secretion.