[CITATION][C] Pharmacology and electrophysiology of ATP-activated ion channels

BP Bean - Trends in pharmacological sciences, 1992 - Elsevier
BP Bean
Trends in pharmacological sciences, 1992Elsevier
Extracellular ATE serves as a messenger in many tissues*. Specific receptors for ATE
mediate a variety of effects, some involving second messenger pathways. In excitable cells,
where ATP acts as a true neurotransmitter, one mechanism is the direct activation of ion
channels. Since the initial discovery in sensory neurons by Krishtal, Marchenko and
Pidoplichko'in 1983, channels activated by external ATE have been found in a variety of
cells. In the past few years, a picture has emerged of a family of channels, located in cell …
Extracellular ATE serves as a messenger in many tissues*. Specific receptors for ATE mediate a variety of effects, some involving second messenger pathways. In excitable cells, where ATP acts as a true neurotransmitter, one mechanism is the direct activation of ion channels. Since the initial discovery in sensory neurons by Krishtal, Marchenko and Pidoplichko’in 1983, channels activated by external ATE have been found in a variety of cells. In the past few years, a picture has emerged of a family of channels, located in cell membranes, that are activated by binding of ATP on the extracellular side. In all cases, the channels are permeable to Na+, K+ and Ca*+, and their opening has a depolarizing, excitatory effect on the cell. Channels in different cells differ in detailed characteristics, including agonist selectivity, size, ion selectivity and desensitization.
Cell types and functions ATE-activated channels are present in a subset of neurons in sensory ganglia of the cat, rat and froe3. So far, voltage-clamp recordings have been possible only in cell bodies, where a functional role for the channels is unlikely. If the channels are also present in afferent nerve endings, they would elicit firing in response to ATP, perhaps serving to report tissue damage. ATP-activated channels are also present in cardiac parasympathetic neurons4. In the CNS, they have been described in dorsal horn neurons’ as well as in a small subset of cultured hippocampal neuror&. In all cases, ATP excites the neurons, but the physiological significance is unknown. ATP-activated channels similar to those in neurons are found in the rat phaeochromocytoma-derived PC12 cell line74, where they can be easily studied.
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