TETRAMETHYLAMMONIUM IS A MUSCARINIC AGONIST IN RAT-HEART

Studies were designed to determine if tetramethylammonium (TMA), a qua ternary amine that structurally resembles the cationic portion of acet ylcholine, can affect cardiac function by acting on muscarinic recepto rs. Experiments examined effects of this cation on 1) the spontaneous beating rate of right atrial preparations isolated from rats, 2) force of contraction in isoproterenol-treated (0.1 mu M) rat papillary musc le, and 3) quinuclidinyl benzilate ([H-3]QNB) binding to rat ventricul ar membranes. TMA elicited concentration-dependent (0.5-50 mM) negativ e chronotropic and negative inotropic actions that were antagonized by the muscarinic receptor antagonist atropine. Radioligand studies show ed that TMA acts as both a competitive and noncompetitive antagonist o f [H-3]QNB binding; the apparent dissociation constant for [H-3]QNB wa s increased (0.092 +/- 0.025 nM in the absence of TMA; 1.14 +/- 0.204 nM in the presence of 50 mM TMA), whereas binding site density was dec reased (148 +/- 26 and 65 +/- 4 fmol/mg in the absence and presence of 50 mM TMA, respectively). These results suggest that extracellular TM A can alter the function of rat heart by stimulating muscarinic recept ors. This action should be considered when using this quaternary amine as a cation substitute.