@article {Shen641, author = {Jian-Bing Shen and Bin Jiang and Achilles J. Pappano}, title = {Lack of Effect of McN-A-343 on Membrane Current and Contraction in Guinea Pig Ventricular Myocytes}, volume = {290}, number = {2}, pages = {641--648}, year = {1999}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {We asked whether agonist occupancy of M1 muscarinic receptor (mAChR) causes increased l-type Ca2+[ICa(L)] and contractions in ventricular myocytes. Voltage-clamp pulses evoked ICa(L) in guinea pig ventricular myocytes superfused with Tyrode{\textquoteright}s solution (22{\textendash}24{\textdegree}C). The mAChR agonists carbachol (Cch, nonselective), McN-A-343 (McN, M1-selective), and oxotremorine (Oxo, M2-selective) were tested at 0.1 mM. None of these agonists affected basal ICa(L). McN did not change isoproterenol-stimulated ICa(L) in 13 of 15 cells. The slight decrease in two cells was not muscarinic because atropine (1 μM) did not antagonize it. Carbachol or Oxo decreased isoproterenol-stimulated ICa(L) by 87 {\textpm} 6.7 (n = 8 cells) and 49 {\textpm} 9.0\% (n = 4 cells), respectively. Atropine blocked inhibition by Cch or Oxo. External stimulation evoked contractions of single myocytes (35{\textdegree}C). McN increased contraction in 1 of 22 cells stimulated at 0.2 Hz and in 0 of 16 cells stimulated at 1.0 Hz. Carbachol significantly increased contraction in 10 of 15 cells at 0.2 Hz and in 8 of 10 cells at 1.0 Hz stimulus frequency. Summarily, the M1-selective agonist McN had a negligible role to regulate ICa(L). The antiadrenergic effect of mAChR agonists is attributable to M2 receptor occupancy. That Cch, but not McN, increased cell shortening excludes participation of M1mAChR in the stimulant effect of Cch on guinea pig ventricular myocyte contractions. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/290/2/641}, eprint = {https://jpet.aspetjournals.org/content/290/2/641.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }