Membrane Potentials

Publication Title: 
Basic & Clinical Pharmacology & Toxicology

Transient receptor potential melastatin 7 (TRPM7) plays a role in a number of physiological and pharmacological functions in variety of cells. The aim of this study was to clarify the role for TRPM7 channels and the effect of waixenicin A on the pacemaking activity of interstitial cells of Cajal (ICCs) and on the cell viability of the human gastric and breast adenocarcinoma cell lines, AGS and MCF-7, respectively.

Author(s): 
Kim, Byung J.
Nam, Joo H.
Kwon, Young K.
So, Insuk
Kim, Seon J.
Publication Title: 
Mechanisms of Ageing and Development

Studies of the yeast Saccharomyces cerevisiae reveal four processes determining life span: metabolism, stress resistance, chromatin-dependent gene regulation, and genome stability. The retrograde response, which signals mitochondrial dysfunction resulting in changes in nuclear gene expression, extends yeast life span and is induced during normal aging. This response involves extensive metabolic adaptations. The retrograde response links metabolism and genome stability during yeast aging. A reduction in the availability of nutrients also extends yeast life span.

Author(s): 
Jazwinski, S. Michal
Publication Title: 
Doklady Akademii nauk SSSR
Author(s): 
Shvets-Ténéta-Guri?, T. B.
Publication Title: 
Anesthesiology

BACKGROUND: Clinical studies suggest that midazolam and propofol interact synergistically to induce hypnosis, but these drugs do not interact synergistically to prevent movement in response to noxious stimuli. The mechanisms underlying these interactions are not certain but may occur at the level of the gamma-aminobutyric acid A (GABA(A)) receptor. METHODS: The authors evaluated the interactions between propofol and midazolam in modulating GABA(A) receptor activity in embryonic hippocampal neurons.

Author(s): 
McAdam, L. C.
MacDonald, J. F.
Orser, B. A.
Publication Title: 
European Journal of Pharmacology

Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABA(A) receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. The potency of TG41 at receptors containing alpha1, beta2, and gamma2L subunits was greater than that of alphaxalone, etomidate, propofol, or pentobarbital.

Author(s): 
Mascia, Maria Paola
Asproni, Battistina
Busonero, Fabio
Talani, Giuseppe
Maciocco, Elisabetta
Pau, Amedeo
Cerri, Riccardo
Sanna, Enrico
Biggio, Giovanni
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Ketamine has important anesthetic, analgesic, and psychotropic actions. It is widely believed that NMDA receptor inhibition accounts for ketamine actions, but there remains a dearth of behavioral evidence to support this hypothesis. Here, we present an alternative, behaviorally relevant molecular substrate for anesthetic effects of ketamine: the HCN1 pacemaker channels that underlie a neuronal hyperpolarization-activated cationic current (I(h)).

Author(s): 
Chen, Xiangdong
Shu, Shaofang
Bayliss, Douglas A.
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

General anesthetics cause sedation, hypnosis, and immobilization via CNS mechanisms that remain incompletely understood; contributions of particular anesthetic targets in specific neural pathways remain largely unexplored. Among potential molecular targets for mediating anesthetic actions, members of the TASK subgroup [TASK-1 (K2P3.1) and TASK-3 (K2P9.1)] of background K(+) channels are appealing candidates since they are expressed in CNS sites relevant to anesthetic actions and activated by clinically relevant concentrations of inhaled anesthetics.

Author(s): 
Lazarenko, Roman M.
Willcox, Sarah C.
Shu, Shaofang
Berg, Allison P.
Jevtovic-Todorovic, Vesna
Talley, Edmund M.
Chen, Xiangdong
Bayliss, Douglas A.
Publication Title: 
Brain Research

Strychnine-sensitive glycine receptors (GlyR) play a major role in the excitability of CNS neurons and are also a major target of many drugs including some general anesthetics and ethanol. The prefrontal cortex (PFC) is an important substrate responsible for cognitive function and for sedation, as well as hypnosis (unconsciousness) which is induced by general anesthetics and ethanol. However, the functions and the physiological and pharmacological properties of GlyRs in mature PFC neurons have not been well studied.

Author(s): 
Lu, Yongli
Ye, Jiang-Hong
Publication Title: 
Neuropharmacology

Thalamocortical (TC) neurons provide the major sensory input to the mammalian somatosensory cortex. Decreased activity of these cells may be pivotal in the ability of general anesthetics to induce loss of consciousness and promote sleep (hypnosis). T-type voltage-gated calcium currents (T-currents) have a key function regulating the cellular excitability of TC neurons and previous studies have indicated that volatile general anesthetics may alter the excitability of these neurons.

Author(s): 
Eckle, Veit-Simon
Digruccio, Michael R.
Uebele, Victor N.
Renger, John J.
Todorovic, Slobodan M.
Publication Title: 
Anesthesia and Analgesia

BACKGROUND: Carboetomidate is an etomidate derivative that produces hypnosis without inhibiting adrenal corticosteroid synthesis. Similar to etomidate, carboetomidate modulates ?-aminobutyric acid type A receptors, but its effects on other ion channel targets of general anesthetics are unknown. METHODS: We compared etomidate and carboetomidate effects on human N-methyl-d-aspartate receptors or neuronal nicotinic acetylcholine receptors (nnAChRs) expressed in Xenopus oocytes, using 2-microelectrode voltage clamp electrophysiology.

Author(s): 
Pierce, David W.
Pejo, Ervin
Raines, Douglas E.
Forman, Stuart A.

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