Article date: July 1999
By: Carlos J Herrero, Esther García‐Palomero, Antonio J Pintado, Antonio G García, Carmen Montiel, in Volume 127, Issue 6, pages 1375-1387
Rat α3β4 or α7 neuronal nicotinic acetylcholine receptors (AChRs) were expressed in Xenopus laevis oocytes, and the effects of various toxins and non‐toxin Ca2+ channel blockers studied. Nicotinic AChR currents were elicited by 1 s pulses of dimethylphenylpiperazinium (DMPP, 100 μM) applied at regular intervals.
The N/P/Q‐type Ca2+ channel blocker ω‐conotoxin MVIIC inhibited α3β4 currents with an IC50 of 1.3 μM; the blockade was non‐competitive and reversible. The α7 currents were unaffected.
At 1 μM, ω‐conotoxin GVIA (N‐type Ca2+ channel blocker) inhibited by 24 and 20% α3β4 and α7 currents, respectively. At 1 μM, ω‐agatoxin IVA (a P/Q‐type Ca2+ channel blocker) did not affect α7 currents and inhibited α3β4 currents by only 15%.
L‐type Ca2+ channel blockers furnidipine, verapamil and, particularly, diltiazem exhibited a preferential blocking activity on α3β4 nicotinic AChRs.
The mechanism of α3β4 currents blockade by ω‐conotoxins and diltiazem differed in the following aspects: (i) the onset and reversal of the blockade was faster for toxins; (ii) the blockade by the peptides was voltage‐dependent, while that exerted by diltiazem was not; (iii) diltiazem promoted the inactivation of the current while ω‐toxins did not.
These data show that, at concentrations currently employed as Ca2+ channel blockers, some of these compounds also inhibit certain subtypes of nicotinic AChR currents. Our data calls for caution when interpreting many of the results obtained in neurons and other cell types, where nicotinic receptor and Ca2+ channels coexist.
Rat α3β4 or α7 neuronal nicotinic acetylcholine receptors (AChRs) were expressed in Xenopus laevis oocytes, and the effects of various toxins and non‐toxin Ca2+ channel blockers studied. Nicotinic AChR currents were elicited by 1 s pulses of dimethylphenylpiperazinium (DMPP, 100 μM) applied at regular intervals.
The N/P/Q‐type Ca2+ channel blocker ω‐conotoxin MVIIC inhibited α3β4 currents with an IC50 of 1.3 μM; the blockade was non‐competitive and reversible. The α7 currents were unaffected.
At 1 μM, ω‐conotoxin GVIA (N‐type Ca2+ channel blocker) inhibited by 24 and 20% α3β4 and α7 currents, respectively. At 1 μM, ω‐agatoxin IVA (a P/Q‐type Ca2+ channel blocker) did not affect α7 currents and inhibited α3β4 currents by only 15%.
L‐type Ca2+ channel blockers furnidipine, verapamil and, particularly, diltiazem exhibited a preferential blocking activity on α3β4 nicotinic AChRs.
The mechanism of α3β4 currents blockade by ω‐conotoxins and diltiazem differed in the following aspects: (i) the onset and reversal of the blockade was faster for toxins; (ii) the blockade by the peptides was voltage‐dependent, while that exerted by diltiazem was not; (iii) diltiazem promoted the inactivation of the current while ω‐toxins did not.
These data show that, at concentrations currently employed as Ca2+ channel blockers, some of these compounds also inhibit certain subtypes of nicotinic AChR currents. Our data calls for caution when interpreting many of the results obtained in neurons and other cell types, where nicotinic receptor and Ca2+ channels coexist.
British Journal of Pharmacology (1999) 127, 1375–1387; doi:10.1038/sj.bjp.0702692
DOI: 10.1038/sj.bjp.0702692
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