The Journal of Neurophysiology Vol. 88 No. 3 September 2002, pp. 1197-1211
Copyright ©2002 by the American Physiological Society

Muscarinic Activation of a Cation Current and Associated Current Noise in Entorhinal-Cortex Layer-II Neurons

 ¹Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada; and  ²Dipartimento di Scienze Fisiologiche-Farmacologiche Cellulari-Molecolari, Sezione di Fisiologia Generale e Biofisica Cellulare, Università degli Studi di Pavia, 27100 Pavia, Italy

Shalinsky, Mark H., Jacopo Magistretti, Li Ma, and Angel A. Alonso. Muscarinic Activation of a Cation Current and Associated Current Noise in Entorhinal-Cortex Layer-II Neurons. J. Neurophysiol. 88: 1197-1211, 2002. The effects of muscarinic stimulation on the membrane potential and current of in situ rat entorhinal-cortex layer-II principal neurons were analyzed using the whole cell, patch-clamp technique. In current-clamp experiments, application of carbachol (CCh) induced a slowly developing, prolonged depolarization initially accompanied by a slight decrease or no significant change in input resistance. By contrast, in a later phase of the depolarization input resistance appeared consistently increased. To elucidate the ionic bases of these effects, voltage-clamp experiments were then carried out. In recordings performed in nearly physiological ionic conditions at the holding potential of 60 mV, CCh application promoted the slow development of an inward current deflection consistently associated with a prominent increase in current noise. Similarly to voltage responses to CCh, this inward-current induction was abolished by the muscarinic antagonist, atropine. Current-voltage relationships derived by applying ramp voltage protocols during the different phases of the CCh-induced inward-current deflection revealed the early induction of an inward current that manifested a linear current/voltage relationship in the subthreshold range and the longer-lasting block of an outward K⁺ current. The latter current could be blocked by 1 mM extracellular Ba²⁺, which allowed us to study the CCh-induced inward current (I_CCh) in isolation. The extrapolated reversal potential of the isolated I_CCh was 0 mV and was not modified by complete substitution of intrapipette K⁺ with Cs⁺. Moreover, the extrapolated I_CCh reversal shifted to approximately 20 mV on removal of 50% extracellular Na⁺. These results are consistent with I_CCh being a nonspecific cation current. Finally, noise analysis of I_CCh returned an estimated conductance of the underlying channels of ~13.5 pS. We conclude that the depolarizing effect of muscarinic stimuli on entorhinal-cortex layer-II principal neurons depends on both the block of a K⁺ conductance and the activation of a "noisy" nonspecific cation current. We suggest that the membrane current fluctuations brought about by I_CCh channel noise may facilitate the "theta" oscillatory dynamics of these neurons and enhance firing reliability and synchronization.