Murali Gopalakrishnan

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Selective modulation of alpha7 nicotinic acetylcholine receptors (nAChRs) is thought to regulate processes impaired in schizophrenia, Alzheimer's disease, and other dementias. One approach to target alpha7 nAChRs is by positive allosteric modulation. Structurally diverse compounds, including PNU-120596,(More)
The cloning and expression of genes encoding for the human neuronal nicotinic acetylcholine receptors (nAChRs) has opened new possibilities for investigating their physiological and pharmacological properties. Cells (HEK 293) stably transfected with two of the major brain subunits, alpha4 and beta2, were characterized electrophysiologically using the(More)
The alpha7 nicotinic acetylcholine receptor (nAChR), a homopentameric, rapidly activating and desensitizing ligand-gated ion channel with relatively high degree of calcium permeability, is expressed in the mammalian central nervous system, including regions associated with cognitive processing. Selective agonists targeting the alpha7 nAChR have shown(More)
BACKGROUND AND PURPOSE Several agonists of the alpha7 nicotinic acetylcholine receptor (nAChR) have been developed for treatment of cognitive deficits. However, agonist efficacy in vivo is difficult to reconcile with rapid alpha7 nAChR desensitization in vitro; and furthermore, the correlation between in vitro receptor efficacy and in vivo behavioural(More)
The focus of the present study is the molecular and functional characterization of four splice variants of the human Nav1.3 alpha subunit. These subtypes arise due to the use of alternative splice donor sites of exon 12, which encodes a region of the alpha subunit that resides in the intracellular loop between domains I and II. This region contains several(More)
(2.4)-Dimethoxybenzylidene anabaseine dihydrochloride (GTS-21), a compound that interacts with rat neuronal nicotinic acetylcholine receptors (nAChRs), was evaluated using human recombinant nAChRs in vitro and various pharmacokinetic and behavioral models in rodents, dogs and monkeys. GTS-21 bound to human alpha 4 beta 2 nAChR (K1-20 nM) 100-fold more(More)
Potassium channels play important roles in vital cellular signaling processes in both excitable and nonexcitable cells. Over 50 human genes encoding various K(+) channels have been cloned during the past decade, and precise biophysical properties, subunit stoichiometry, channel assembly, and modulation by second messenger and ligands have been elucidated to(More)
The present study investigated the effects of iberiotoxin (IbTx), a peptide toxin blocker of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels and NS1619, a BK(Ca) channel opener, on action potential firing of small and medium size afferent neurons from L6 and S1 dorsal root ganglia of adult rats. Application of IbTx (100 nM) reduced whole-cell(More)
ABT-594 and A-582941 are high affinity neuronal nicotinic acetylcholine receptor agonists with differential selectivity for the alpha4beta2 and the alpha7 subtypes, respectively. This study was designed to determine whether either compound, like nicotine also possesses cognitive-enhancing ability. The compounds were administered by intramuscular injection(More)
KCNQ2/3 voltage-gated potassium channels conduct low-threshold, slowly activating and non-inactivating currents to repolarize the neuronal resting membrane potential. The channels negatively regulate neuronal excitability and KCNQ2/3 openers are efficacious in hyperexcited states such as epilepsy and pain. We developed and utilized thallium influx assays to(More)