Muscarinic cation channels

The EOs reduced the contraction induced by acetylcholine, histamine [226-228, 210, 225, 232, 233], carbachol (muscarinic receptor activator) [237] and 5-hydroxytryptamine [229]. The EOs were found to relax intestinal smooth muscle by reducing the influx of Ca [227, 234], K+ [210, 224-226, 229, 230] and Ba [229, 237]. However, other reports have shown that lavender and geranium EOs were unlikely to act as cationic channel blockers [232]. The activities of the EOs resembled those of dicyclomine and atropine (muscarinic receptor antagonists) and dihydropyridine (calcium antagonist) by producing smooth-muscle relaxation [225, 236]. 

Answer C. Muscarinic receptors present in bronchiolar smooth muscle are of the M3 subtype coupled via Gq proteins to phospholipase C. Activation of this enzyme causes hydrolysis of phosphatidylinositol bisphosphate, with release of IP3 and DAG (the latter activates protein kinase C). Decreased formation of cAMP mediated via a G protein occurs with activation of M2 receptors such as those in the heart. Cation channel opening occurs in response to activation of nicotinic receptors. 

Answer A. ACh receptors in the CNS are present on less than 5% of the neuronal population. Most of them are of the muscarinic subtype, M (excitatory) and M2 (inhibitory), via G-protein coupled changes in cAMP. Nicotinic receptors are excitatory via direct coupling to cation channels (Na/K), and their activation does not initiate second messenger pathways. Other CNS transmitter receptors that are directly coupled to ion channels include those for GABA and glutamic add. Almost all CNS receptors for DA, NE, 5HT, and opioid peptides are coupled to ion channels via second messenger systems. 

A classic example of a ligand-gated ion channel from the cys-loop superfamily is the nAChR. The nicotinic AChRs are named so because they can be activated by the tobacco alkaloid nicotine in the same way they are activated by ACh. It should be mentioned that the muscarinic A.ChR s, which respond to the alkaloid muscarine, are not ion channels, and therefore not discussed in this chapter. The nAChR is made up of five subunits (al, pi, 7, 5, and e) with two binding sites for ACh (Figures 16.6B and 16.9). The nAChRs are expressed in nerves and skeletal muscle (but not smooth muscle) and play an important role in the fast synaptic transmission in synaptic neuronal-neuronal and neuromuscular junctions. nAChR is a nonselective cation channel that allows the flow of many cations, but not anions. After ACh binds to the nAChR it allows Na" " and also Ca " ", to flow down their electrochemical gradient into the cell, which depolarizes the cell membrane and generates an action potential (Figure 16.6B). 

Metabotropic Cation Channels Activated by Muscarinic Receptors... 

One major question relates to whether the nonselective cation channels activated by norepinephrine and acetylcholine are the same protein. Inoue and Kuriyama (Inoue and Kuriyama 1993) studied the activation of both currents in the rabbit portal vein, one of the few vascular preparations in which excitatory muscarinic responses are observed. Based on lack of an additional current response once Icat was fully activated by one agonist, and similar current I-V relationships, current activation and deactivation kinetics, single channel conductance, and block by Cd they concluded that adrenergic and muscarinic stimulation activates a common nonselective cation channel. On the other hand, substantial differ-... 

Ketamine appears to act similarly to phencyclidine (PCP also known as Angel Dust), which acts as an antagonist within the cationic channel of the NMDA receptor complex (36). By preventing the flow of cations through this channel, ketamine prevents neuronal activation, which normally is required for the conscious state. The analgesic activity of ketamine, however, is more likely the result of an interaction with an opioid receptor or the less-well-understood o-receptor. Other studies have suggested a possible involvement of serotonin receptors and muscarinic receptors (37). Ketamine, like PCP, has a significant potential for abuse. 

Haj-Dahmane S, Andrade R 1996 Muscarinic activation of a voltage-dependent cation nonselective current in rat association cortex. J Neurosci 16 3848-3861 Hardie RC, Minke B 1993 Novel Ca2+ channels underlying transduction in Drosophila photoreceptors implications for phosphoinositide-mediated Ca2+ mobilization. Trends Neurosci 16 371-376... 

Two distinct receptor groups have been identified for acetylcholine, the nicotinic and the muscarinic groups (Table 11.1). Furthermore, there are at least four subtypes of nicotinic and five subtypes of muscarinic receptors. Nicotinic receptors are ubiquitous and exist at the neuromuscular junctions of skeletal muscles and on ganglion cells in the autonomic nervous system. Nicotinic receptors located on cation-specific ion channels, when opened, evoke fast, transient depolarizations of the recipient cell. Muscarinic receptors are found in smooth muscle receiving parasympathetic innervation and elsewhere, and can be blocked by atropine. Muscarinic receptors are coupled indirectly to slow and fast ion channels via G proteins. 

Inoue, R. and Kuriyama, H. (1993) Dual regulation of cation-selective channels by muscarinic and alpha 1-adrenergic receptors in the rabbit portal vein. Journal of Physiology, 465 427-448,... 

The mechanisms of all the neurotransmitters function have not been well understood. One neurotransmitter, acetylcholine, has been studied intensely and will be discussed briefly here. The structure of acetylcholine is shown in Fig. 17.2, along with those of nicotine, serotonin and muscarine. Acetylcholine is released from the synapse and migrates to the next neuron surface nearby, and binds to a receptor. There are two types of acetylcholine receptor one is nicotinic , implying that it also binds nicotine, and the other muscarinic . Nicotine and muscarine (as seen in Fig. 17.2) have a common feature, i.e., a positively charged nitrogen such as acetylcholine. The receptor itself is an ion channel. When acetylcholine binds with the receptor, the ion channel opens up, and the inflow of Na and outflow of K ensues. The sudden change of the cationic concentration inside and outside of the postsynaptic neuron creates an... 

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