Cellular mechanisms underlying two muscarinic receptor-mediated depolarizing responses in relay cells of the rat lateral geniculate nucleus

Abstract

We used the whole-cell recording technique in an in vitro preparation to examine the electrophysiological actions of the muscarinic receptors on relay cells in the rat lateral geniculate nucleus. Drop application of the muscarinic agonist acetyl- β-methylcholine resulted in a slow depolarization that persisted for several minutes. The response was insensitive to the nicotinic antagonist hexamethonium, but was blocked by atropine, a muscarinic antagonist. The response was also insensitive to blockade of synaptic transmission by tetrodotoxin, indicating a direct muscarinic effect. The muscarinic depolarization consisted of two components that were somewhat separated in time. The early portion of the muscarinic response was mediated by a large inward current with little change in input resistance, while the later portion was mediated by a small inward current associated with a large increase in input resistance. Pharmacological agents were used to distinguish the two components. Drop application of McN-A-343, an m1 receptor agonist, could only mimic the later component of the muscarinic response. This was supported by the result that the later component was blocked by low concentrations of pirenzepine. These data suggest that the m1 receptor only mediates the late component of the muscarinic response, while the early component is mainly mediated by the m3 receptor. The idea that both m1 and m3 receptors were involved in the muscarinic depolarization was further supported by voltage-clamp analysis. This revealed that activation of the m1 receptor was associated with a decrease in an inward potassium current, I Kleak, while activation of the m3 receptor was likely associated with both a decrease in I Kleak and an increase in the hyperpolarization-activated cation current I h. In summary, our data suggest that muscarinic responses in geniculate relay cells result from the activation of two receptors, which modulate I Kleak and I h. Given the fact that the ascending aminergic systems also depolarize geniculate relay cells via two receptors acting on I Kleak and I h, we concluded that ascending activating systems use common mechanisms to enact the depolarizing form of arousal in relay neurons.