Neuron depolarization

Synaptic vesicles are the organelles in axon terminals that store neurotransmitters and release them by exocytosis. There are two types, the large dense-core vesicles, diameter about 90 nm, that contain neuropeptides, and the small synaptic vesicles, diameter about 50nm, that contain non-peptide transmitters. About ten vesicles per synapse are docked to the plasma membrane and ready for release, the readily releasable pool . Many more vesicles per synapse are stored farther away from the plasma membrane, the resting pool . When needed, the latter vesicles may be recruited into the readily releasable pool. Neuronal depolarization and activation of voltage-sensitive Ca2+... 

Surprisingly few studies have been performed with purified toxins. When added externally to the water, toxins of various origins were tested on the cope-pod Tigriopus californicus. The protein phosphatase inhibitor okadaic acid (17) from red tide dinoflagellates [22] and the neuronal depolarizing agent do-moic acid (10) from diatoms [40, 41] had different effects on the herbivores (Scheme 3). Micromolar concentrations of okadaic acid (17) acted both as toxin... 

Endocannabinoids are endogenous ligands for the CB1 receptor. The best established are anandamide (N-arachidonoylethanolamine) and 2-AG (2-arachidonoyl-glycerol). Others may also exist. Pathways involved in the formation and inactivation of anandamide and 2-AG are shown in Figure 56-6. Some steps in their formation are Ca2+-dependent. This explains the ability of neuronal depolarization, which increases postsynaptic intracellular Ca2+ levels, to stimulate endocannabinoid formation and release. Some neurotransmitter receptors (e.g. the D2 dopamine receptor) also stimulate endocannabinoid formation, probably by modulating postsynaptic Ca2+ levels or signaling pathways (e.g. PLC) that regulate endocannabinoid formation. 

Reserpine blocks vesicular storage of monoamines, prolonging their presence in cytoplasm. There they are degraded by MAO, leading to a depletion of monoamines in synaptic terminals of central and peripheral neurons, so that little or no neurotransmitter is released when the neuron depolarizes (Oates 1996). Reversal of this process requires synthesis of new vesicles, which occurs over a period of days to weeks after discontinuation of the drug. 

Suppose that a specific neurotransmitter arrives at its ligand-gated ion channel, say a sodium ion channel. It will open and sodium ions will flow into the postsynaptic neuron, depolarizing its membrane. If this depolarization exceeds the threshold level, this will open voltage-gated sodium and potassium ion channels, generating an action potential that will flow down the dendrite to the cell body, and so on. 

With TMS, a brief but powerful electric current is passed through a small coil held against the scalp of a conscious patient. This generates a powerful local magnetic field which passes unimpeded through the skull and induces a weaker, less focused electric current within the brain. Due to the non-invasive nature of this method, the important physiological effects of TMS are likely to be a consequence of the density of the electric current and the electric field which is induced in the cortex. It is believed that the induced electrical fields cause neuronal depolarization which changes the neurotransmitter release mechanisms. 

Treatment of neuronal cultures with glutamate is accompanied by the loss of neuronal viability, reduced neuronal energy state (ATP level and mitochondrial membrane potential), and increased cytoplasmic mitochondrial Ca2+. This decrease in ATP results in failure of ionic pumps and increase in extracellular K+. These processes cause neuronal depolarization and release of glutamate, which over-stimulates NMDA receptors. The NMDA antagonist MK-801... 

Ohno-Shosaku T, MaejimaT, Kano M (2001) Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron 29 729-38 Ohno-Shosaku T, Shosaku J, Tsubokawa H, Kano M (2002) Cooperative endocannabinoid production by neuronal depolarization and group I metabotropic glutamate receptor activation. Eur J Neurosci 15 953-61... 

Immediately after the onset of focal brain ischemia, oxygen and glucose deprivation result in loss of adenosine triphosphate (ATP), loss of maintenance of normal ion channels and neuronal depolarization (Wahlgren and Ahmed, 2004) as evidenced by calcium and sodium influx into the cells. 

Recent studies have also shown that neuronal depolarization will cause increases in Tj and T. T was shown to increase by 13% while T2 increased by 88% at 1.5 T in a rat model of spreading depression (Stanisz et al., 2002). While... 

NE is synthesized by tyrosine hydroxylation (meta ring position) followed by decarboxylation and side chain p carbon hydroxylation. The synthesis of this catecholamine is regulated by tyrosine hydroxylase. Tyrosine hydroxylation is also a key step in the synthesis of two other important catecholamines, dopamine and epinephrine. NE is packaged via active transport into synaptic (or chromaffin) vesicles prior to release by neuronal depolarization. The effects of NE are mediated by adrenergic receptors (a or P) which are G protein coupled resulting in either increases or decreases in smooth muscle tone as well as increases in cardiac rate and contractility. These effects arise out of receptor mediated increases in intracellular Ca and activation or inhibition of various protein kinases. The effects of NE are terminated essentially as a result of its active transport into the presynaptic nerve ending via an energy and Na" dependent process which utilizes the norepinephrine transporter (NET). Ultimately, NE and other catecholamines are metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). 

Stanisz GJ, Yoon RS, Joy ML, Henkelman RM (2002) Why does MTR change with neuronal depolarization Magn Reson Med 47 472 75. 

Alosetron is a potent and selective 5-HT3 receptor antagonist. 5-HT3 receptors are nonselective cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. 5-HT3 receptor antagonists such as alosetron inhibit activation of these channels that results in the modulation of the enteric nervous system. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions, processes that relate to the pathophysiology of IBS. 

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