Neuron ionotropic receptors

FIGURE 2.3 Glutamatergic synapse. Glutamate binds to ionotropic receptors (1) and metabotropic receptors (2). The glutamate transporter (3) pumps glutamate back into the glutamatergic neuron. 

Whereas membrane-delimited actions occur within microdomains in the membrane, second messenger-mediated effects can occur over considerable distances. Finally, an important consequence of the involvement of G proteins in receptor signaling is that, in contrast to the brief effect of ionotropic receptors, the effects of metabotropic receptor activation can last tens of seconds to minutes. Metabotropic receptor predominate in the diffuse neuronal systems in the CNS (see below). 

Figure 30-19 Major signaling pathways from metabotropic and ionotropic receptors in neurons. Various G proteins control the signaling from mutabo-tropic receptors using phosphatidylinisitol-specific phospholipase C (PI-PLC) and adenylate cyclase or acting directly on K+ ion channels. Adapted from Fig. 5.1 of Nicholls Proteins, Transmitters, and Synapses.149...

Information transfer between two neurons or between neurons and effector cells involves the release of chemical substances, which then act on the target cell by binding to appropriate receptors embedded in the plasma membrane. This process, as originally described by Otto Loewi (Loewi 1921), is termed chemical neurotransmission and occurs at contact sites known as synapses. Neurotransmitters exert their effects via members of two major families of receptors ionotropic and metabotropic neurotransmitter receptors. Activation of ionotropic receptors leads to an increase in the ion conductance of the membrane within a time scale of milliseconds or even less, whereas activation of metabotropic receptors results in slow effects (within seconds or even minutes) which involve more or less complex signaling cascades. Accordingly, information transfer via ionotropic receptors is called fast synaptic transmission, whereas the slow counterpart is called neuromodulation (Kaczmarek and Levitan 1987). 

Mode of action. The precise mode of action of carbamazepine has not been fully established. It has been shown to stabilize both pre- and postsynaptic neurons by blocking the use and frequency-dependent sodium channels. While this is probably its main action, the blockade of the glutamate NMDA ionotropic receptors also leads to a reduction in the influx of sodium and calcium ions into the neuron. The net effect of these changes is a reduction in the sustained high-frequency repetitive firing of the action potentials which characterize epileptic activity. There is also evidence that carbamazepine blocks purine, noradrenaline, serotonin and muscarinic acetylcholine receptors which probably accounts for the use of carbamazepine as a mood stabilizing agent. 

Accumulating findings indicate that nucleotides play an important role in neuron-to-glia communication through P2 purinoceptors. P2 purinoceptors are divided into two families, ionotropic receptors (P2X) and metabotropic receptors (P2Y). P2X receptors (seven types P2X]-P2X7) contain intrinsic pores that open... 

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