Neuronal activity, types

Extracellular ATP has been demonstrated to activate a depolarizing current in different neuronal and non-neuronal cell types. These receptors are also referred to as P2 receptors. The receptors can further be divided into the G-protein-coupled P2Y receptors and the ligand-gated ion channels P2X. Currently, seven P2X receptors (P2XJ-P2X- ) have been cloned (Table 3.3). The receptors exhibit between 26 and 50% overall amino-acid identities, with the highest level of conservation in the extracellular and transmembrane regions. P2X7 (also called P2Z) is the most distant member of the family. 

These studies could be categorized into three types (1) Measurement of HA release and turnover, (2) measurement of c-Fos protein as a marker of neuronal activation, and (3) measurement of sleep-wakefulness in HDC knockout mice that cannot synthesize HA. 

With this in mind, the search for molecular markers that define populations of neurons in areas important for arousal is clearly warranted. In this chapter we describe the identification of four peptidergic systems that modulate different aspects of the sleep-wakefulness cycle. The success of this strategy demonstrates the need for new markers of neuronal cell types, which may define populations of neurons critical for our understanding of cortical activity and sleep. 

P2Y receptors are activated by adenine and uridine nucleotides. Most of the known P2Y receptors have been detected in the nervous system [21]. The majority of P2Y receptors inhibit neuronal N-type Ca2+ channels and M-type K+ channels. P2Y1 receptors are found exclusively on platelets, on their precursor megakaryocyte cells and on certain other cultured hematopoietic cells, such as K562 leukemia cells. They can be distinguished from other P2 receptors in that ADP is the most potent natural agonist and ATP is a competitive antagonist. ADP acts via a G protein to inhibit cyclic AMP accumulation, mobilize intracellular Ca2+ and stimulate granule secretion. ADP... 

In addition to the selective responses of adenylyl cyclases to GPy subunits, it is likely that different forms of Gp and Gy subunits influence the various forms of adenylyl cyclase in different ways [19]. There are five known forms of Gp subunits and 11 known forms of Gy subunits (see Ch. 19). Differential expression and regulation of these subunits could provide still additional mechanisms for selectively controlling adenylyl cyclase catalytic activity in specific neuronal cell types. 

Tatulian, L., Delmas, P., Abogadie, F. C., Brown, D. A. Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine, The Journal of Neuroscience 2001, 21, 5535-5545. 

Epilepsy is a chronic neurologic disorder characterized by recurrent seizures.33 Seizures are episodes of sudden, transient disturbances in cerebral excitation that occur when a sufficient number of cerebral neurons begin to fire rapidly and in synchronized bursts.42 Depending on the type of seizure, neuronal activity may remain localized in a specific area of the brain, or it may spread to other areas of the brain. In some seizures, neurons in the motor cortex are activated, leading to skeletal muscle contraction via descending neuronal pathways. These involuntary, paroxysmal skeletal muscle contractions seen during certain seizures are referred to as convulsions. However, convulsions are not associated with all types of epilepsy, and other types of seizures are characterized by a wide variety of sensory or behavioral symptoms. 

K+ channels are responsible for setting the resting membrane potential and for the repolarizing phase of action potentials. In addition, K+ channels mediate afterhyperpolarizations to terminate periods of high neuronal activity and to modulate firing rates. When located in presynaptic nerve terminals, these actions of K+ channels will contribute to the regulation of transmitter release. In fact, most types of the huge superfamily of K+ channels, in particular delayed rectifier, fast transient, and Ca2+-sensitive K+ channels, have been found in a variety of nerve terminals and... 

Presynaptic receptor that is activated by a neurotransmitter from an adjacent neuron the type of neurotransmitter activating the heteroceptor differs from that released from the axon. 5-Hydroxyindoleacetic acid, the main metabolite of 5-hydroxytryptamine (serotonin) formed by monoamine oxidase. 

Fig. 4. 5-HT neuron activity and 5-HT release in wild-type (WT) and 5-HT1A knockout (KO) mice in response to the systemic administration of the 5-HT1A agonist 8-OH-DPAT and the SSRI fluoxetine. (A,C) 8-OH-DPAT inhibited the firing rate of...

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