Biomedical subjects

N Burnashev

Publications and source records attributed to N Burnashev.

40 records · Page 3Linked to original sources

PubMed1990

Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS.

In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). In each member of a family of four abundant AMPA receptors, a small segment preceding the predicted fourth transmembrane region has been shown to exist in two versions with different amino acid sequences. These modules, designated "flip" and "flop," are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate. For each receptor, the alternatively spliced messenger RNAs show distinct expression patterns in rat brain, particularly in the CA1 and CA3 fields of the hippocampus. These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.

Amino Acid Sequence↗

PubMed1990

Quinidine blocks adenosine 5'-triphosphate-sensitive potassium channels in heart.

The ATP-sensitive potassium channel current (IK-ATP) was studied in excised inside-out patches from rat ventricular cells at 20-23 degrees C. The bath solution contained 140 mM KF, and the pipette solution contained 140 mM KCl and 1.2 mM MgCl2. ATP (0.5 mM) in the bath inhibited IK-ATP. In the absence of ATP, 10 microM quinidine decreased open probability 67 +/- 1% (n = 6) at -50 mV and 28 +/- 12% at -130 mV (n = 5) without affecting single channel conductance (48-52 pS). The block increased with 25 and 50 microM quinidine and could be reversed on washing quinidine for several minutes. Interburst (closed) intervals were increased by quinidine, whereas open and closed time distributions within bursts were not changed. We conclude that quinidine blocks IK-ATP in a "slow" and voltage-dependent manner in clinically relevant concentrations. Because of the postulated role for IK-ATP in cardiac ischemia, quinidine block of this channel may play a role in ischemic arrhythmias.

Adenosine Triphosphate↗

PubMed1988

Gating kinetics of ATP-sensitive single potassium channels in myocardial cells depends on electromotive force.

ATP-sensitive single-channel potassium currents were studied in the membrane of rat ventricular myocytes. With an internal K+ concentration of [K+]i = 140 mM, the outwardly directed currents saturated at approximately 1.8 pA in the region of positive potentials independently of the external K+ concentration [K+]o, whereas an increase in [K+]i of up to 300 mM caused a positive shift in the region of current saturation (from approximately +40 mV to approximately +100 mV) and an increase in the level of the saturation up to approximately 4 pA. The openings of the channels appeared in bursts. Gating kinetics within the bursts were investigated. It was shown that the channel mean open (tau o) and closed (tau c) times during a burst depended primarily on the electromotive force (V-Vk) for potassium ions. For different [K+]o, tau o was maximal and tau c was minimal in the region of reversal potentials (Vrev); tau o decreased and tau c increased gradually with deviation of V from Vrev. Therefore we conclude that the gating properties of the ATP-sensitive K channels depend on the ion flux parameters.

Adenosine Triphosphate↗

PubMedDate not supplied

Calcium permeability of ligand-gated channels.

Ligand-gated channels activated by excitatory neurotransmitters: glutamate, acetylcholine, ATP or serotonin are cation channels permeable to Ca2+. Molecular cloning revealed a large variety of the ligand-gated channel subunits differentially expressed in mammalian brain. Many of them have different Ca2+ permeability providing immense diversity in Ca2+ entry mediated by ligand-gated channels during synaptic transmission. Functional analysis of cloned channels allowed to identify structural elements in the pore forming regions determining Ca2+ permeability for many types of ligand-gated channels. The functional role of the Ca2+ entry mediated by various ligand-gated channels in mammalian central nervous system is less understood. The studies reviewed in this article provide information about known structural determinants of Ca2+ permeability of the ligand-gated channels and the role of this particular pathway of Ca2+ entry in cell function.

Adenosine Triphosphate↗