MUSCARINIC RECEPTOR-MEDIATED INHIBITION OF VOLTAGE-ACTIVATED CA CURRENT IN NEUROBLASTOMA X GLIOMA HYBRID (NG-108-15) CELLS - REDUCTION OF MUSCARINIC AGONIST AND ANTAGONIST POTENCY BY TETRAETHYLAMMONIUM (TEA)

Patch clamp techniques were used to record voltage-activated Ca currents from NG 108-15 cells. The muscarinic agonists acetylcholine (ACh) and oxotremorine-M partially inhibited the Ca current (mean inhibition 37%) with EC50 values of 0.32-mu-M and 0.14-mu-M, respectively. The EC50 for ACh in the presence of neostigmine (1-mu-M) was 0.11-mu-M. Tetraethylammonium (TEA) (10 mM) shifted ACh (+ neostigmine) and oxotremorine dose-response curves to the right by 36- and 20-fold, respectively. TEA also inhibited muscarinic receptor binding (K(i) values in brackets) of (i) N-methyl scopolamine ([H-3]NMS) to homogenates of rat heart (86-mu-M) and rat submandibular gland (178-mu-M) and to intact NG 108-15 cells (358-mu-M) and (ii) [H-3]pirenzepine binding to rat cerebral cortex homogenates (111-mu-M). Atropine antagonized muscarinic agonist responses and was found to have a pK(B) of 9.8 +/- 0.39, but 10 mM TEA reduced the potency of atropine by 69-fold, probably because of the weak antagonist action of TEA.