Effects of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic acetylcholine receptors on transmembrane potentials and currents in guinea pig ventricular myocytes
✍ Scribed by Rongrui Zhao; Wenze Wang; Bowei Wu; Johan Hoebeke; Åke Hjalmarson; Michael L. X. Fu
- Publisher
- Springer
- Year
- 1996
- Tongue
- English
- Weight
- 697 KB
- Volume
- 163-164
- Category
- Article
- ISSN
- 0300-8177
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✦ Synopsis
The effects of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptor on transmembrane potentials and currents in guinea pig single ventricular cells were analyzed using whole-cell patch clamp technique. These effects were compared with those of the muscarinic receptor agonists carbachol and acetylcholine. The antibodies shortened the action potential duration in a dose-dependent manner. By using a ramp or step rectangular pulse protocol, it was found that the antibodies increased the outward K ÷ current and decreased the inward basal Ica significantly. The reversal potential of both carbachol-and antibody-induced extra currents were close to -80 mV, being in proximity to the calculated E k of-90 mV. A [3-adrenergic receptor agonist, isoprenaline, prolonged the action potential and increased the overshoot which could be inhibited by both antibody and carbachol. Isoprenaline increased inward Ica and outward I k simultaneously. Both antibody and carbachol could significantly reduce the isoprenaline-stimulated Ica but not the isoprenaline-stimulated I k. The antibody-or carbachol-induced outward K + current and the depressant effects of antibody and carbachol on isoprenaline-stimulated Ica were partially antagonized by atropine. These results suggest that the anti-M2 muscarinic receptor antibodies display a stimulatory activity similar to muscarinic receptor agonist on the receptor-mediated electrophysiological events. (Mol Cell B iochem 163/164:185-193, 1996)