Cuevas, J. and Adams, D. J. M 4 muscarinic receptor activation (mAChR)-induced voltage responses have been observed modulates calcium channel currents in rat intracardiac neurons. J. in guinea pig intracardiac neurons: two temporally distinct Neurophysiol. 78: 1903Neurophysiol. 78: -1912Neurophysiol. 78: , 1997. M odulation of high-voltagedepolarizations and a slow hyperpolarization (Allen and activated Ca 2/ channels by muscarinic receptor agonists was inves- Mihara et al. 1988 ). The faster

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... polarizatigated in isolated parasympathetic neurons of neonatal rat intracartion is believed to be associated with a decrease in K / perdiac ganglia using the amphotericin B perforated-patch whole cell meability, whereas the slower depolarization and the hyperrecording configuration of the patch-clamp technique. Focal applipolarization with increases in a Cl 0 and a K / conductance, cation of the muscarinic agonists acetylcholine (ACh), muscarine, respectively (Allen et al. 1994) . Acetylcholine (ACh) actiand oxotremorine-M to the voltage-clamped soma membrane reversibly depressed peak Ca 2/ channel current amplitude. The dose-vation of muscarinic receptors also decreases the amplitude reponse relationship obtained for ACh-induced inhibition of Ba 2/ of the tetrodotoxin (TTX) -insensitive component of the current (I Ba ) exhibited a half-maximal inhibition at 6 nM. Maximal action potential and Ca 2/ -dependent afterhyperpolarization inhibition of I Ba amplitude obtained with 100 mM ACh was Ç75% in guinea pig cultured intracardiac neurons (Allen and Burncompared with control at /10 mV. Muscarinic agonist-induced stock 1990), consistent with a decrease in Ca 2/ influx attenuation of Ca 2/ channel currents was inhibited by the muscathrough voltage-dependent Ca 2/ channels. Inhibition of derinic receptor antagonists pirenzepine (°300 nM) and m4-toxin polarization-activated Ca 2/ channel currents by muscarine (°100 nM), but not by AF-DX 116 (300 nM) or m1-toxin (60 has been observed in mammalian central and peripheral neu-nM). The dose-response relationship obtained for antagonism of rons, including sympathetic neurons of rat superior cervical muscarine-induced inhibition of I Ba by m4-toxin gave an IC 50 of 11 nM. These results suggest that muscarinic agonist-induced inhiganglia Wanke et al. 1987) and rat bition of high-voltage-activated Ca 2/ channels in rat intracardiac hippocampal pyramidal neurons (Ga ¨hwiler and Brown neurons is mediated by the M 4 muscarinic receptor. M 4 receptor 1987). Muscarinic receptor-mediated Ca 2/ channel inhibiactivation shifted the voltage dependence and depressed maximal tion has also been observed in amphibian parasympathetic activation of Ca 2/ channels but had no effect on the steady-state neurons of the interatrial septum of the bullfrog heart (Tse inactivation of Ca 2/ channels. Peak Ca 2/ channel tail current amet al. 1990). However, muscarinic receptor modulation of plitude was reduced ¢30% at /90 mV in the presence of ACh, voltage-dependent Ca 2/ channels has not been investigated indicating a voltage-independent component to the muscarinic in parasympathetic neurons of mammalian intracardiac ganreceptor-mediated inhibition. Both dihydropyridine-and v-conotoxin GVIA-sensitive and -insensitive Ca 2/ channels were inhib-glia. ited by ACh, suggesting that the M 4 muscarinic receptor is coupled