Differential blockade of rat α3β4 and α7 neuronal nicotinic receptors by ω‐conotoxin MVIIC, ω‐conotoxin GVIA and diltiazem

摘要: Rat α3β4 or α7 neuronal nicotinic acetylcholine receptors (AChRs) were expressed in Xenopus laevis oocytes, and the effects of various toxins non-toxin Ca2+ channel blockers studied. Nicotinic AChR currents elicited by 1 s pulses dimethylphenylpiperazinium (DMPP, 100 μM) applied at regular intervals. The N/P/Q-type blocker ω-conotoxin MVIIC inhibited with an IC50 1.3 μM; blockade was non-competitive reversible. The unaffected. At 1 μM, GVIA (N-type blocker) 24 20% currents, respectively. At ω-agatoxin IVA (a P/Q-type did not affect only 15%. L-type furnidipine, verapamil and, particularly, diltiazem exhibited a preferential blocking activity on AChRs. The mechanism ω-conotoxins differed following aspects: (i) onset reversal faster for toxins; (ii) peptides voltage-dependent, while that exerted not; (iii) promoted inactivation current ω-toxins not. These data show that, concentrations currently employed as blockers, some these compounds also inhibit certain subtypes currents. Our calls caution when interpreting many results obtained neurons other cell types, where receptor channels coexist. British Journal Pharmacology (1999) 127, 1375–1387; doi:10.1038/sj.bjp.0702692