Biomedical subjects

M Kanazirska

Publications and source records attributed to M Kanazirska.

7 recordsLinked to original sources

PubMed1997

Voltage-dependent effect of Al3+ on channel activities in hippocampal neurons.

The effects of Al3+ on Na+ and K+ channel activities in rat and rabbit hippocampal neurons have been examined. Al3+ mediated a pronounced voltage-dependent inhibition of single Na+ channel activities in inside-out patches excised from neuronal membranes. The reduction in channel activity was more substantial under defined conditions, particularly when changing the holding potential from -120 to -80 mV. This voltage-dependent block indicates that Al3+ can mainly inhibit the excitation of neurons with less negative resting potentials. The observed effect may be related to the pathogenetic mechanism of the specific action of Al3+ on defined types of neurons affected in neurodegenerative disorders such as Alzheimer's disease.

Aluminum↗

PubMed1997

Amyloid-beta proteins activate Ca(2+)-permeable channels through calcium-sensing receptors.

The amyloid-beta peptides (A beta) are produced in excess in Alzheimer's disease (AD) and may contribute to neuronal dysfunction and degeneration. This study provides strong evidence for a novel cellular target for the actions of A beta, the phospholipase C-coupled, extracellular Ca(2+)-sensing receptor (CaR). We demonstrate that A beta(s) produce a CaR-mediated activation of a Ca(2+)-permeable, nonselective cation channel (NCC), probably via elevation in cytosolic Ca2+ (Cai), in cultured hippocampal pyramidal neurons from normal rats and from wild type mice but not those from mice with targeted disruption of the CaR gene (CaR -/-). A beta(s) also activate NCC in CaR-transfected but not in nontransfected human embryonic kidney (HEK293) cells. Thus aggregates of A beta deposited on hippocampal neurons in AD could appropriately activate the CaR, stimulating Ca(2+)-permeable channels and causing sustained elevation of Cai with resultant neuronal dysfunction.

Amyloid beta-Peptides↗

PubMed1997

Assessment of frequency-dependent alterations in the level of extracellular Ca2+ in the synaptic cleft.

The synaptic cleft may be represented as a very thin disk of extracellular fluid. It is possible that at high stimulation frequencies the interval between pulses would be insufficient for diffusion of Ca2+ from the periphery of the cleft to replace extracellular Ca2+ depleted at the center of the cleft as a result of activation of postsynaptic, Ca2(+)-permeable channels. Computer modeling was employed to assess the impact of activation of glutamate receptor channels (GRCs) in the postsynaptic membrane on the level of extracellular Ca2+ within the synaptic cleft. The model includes calcium influx from the synaptic cleft into the postsynaptic compartment through GRC and calcium efflux through calcium pumps and Na/Ca exchangers. Concentrations of extracellular Ca2+ inside the cleft are estimated by using a compartmental model incorporating flux across the postsynaptic membrane and radial diffusion from the edges of the cleft. The simulations suggest that substantial extracellular Ca2+ depletion can occur in the clefts during activation of GRCs, particularly at high stimulation frequencies used to induce long-term potentiation (LTP). Only minimal transitory changes in extracellular Ca2+ are observed at low frequencies. These frequency-dependent alterations in extracellular Ca2+ dynamics are a direct reflection of the activity of GRCs and could be involved in the modulation of presynaptic function via a retrograde messenger mechanism, if there are extracellular Ca2+ sensors on the presynaptic membranes. The recently cloned extracellular Ca2(+)-sensing receptors that are known to be present in nerve terminals in hippocampus and other areas of the brain could potentially play such a role.

Calcium↗

PubMed1997

Deficient cation channel regulation in neurons from mice with targeted disruption of the extracellular Ca2+-sensing receptor gene.

This study presents evidence that a receptor sensitive to the concentration of extracellular Ca2+ (Ca[2+]o) (CaR) is functionally coupled to ion channels involved in modulation of neuronal excitability. This receptor is expressed in hippocampus and other brain regions, suggesting that it could mediate some of the well-recognized but poorly understood direct actions of extracellular Ca2+ (Ca[2+]o) on neuronal function. The effects of polycationic CaR agonists on the activity of a nonselective cation channel (NCC) in cultured hippocampal neurons from wild-type mice and from mice homozygous for targeted disruption of the CaR gene (CaR -/-) were compared in this study. The CaR agonists, neomycin (100 microM), spermine (300 microM), and elevation of Ca(2+)o from 0.75 to 3 mM, significantly increased the probability of channel opening (Po) in wild-type neurons. None of these agents, however, produced any effect on Po in neurons from mice lacking the CaR. The same NCC, however, could be activated by thapsigargin in neurons from both wild-type mice and CaR-deficient mice, most likely through an associated increase in the cytosolic free calcium concentration (Ca[i]). Thus the CaR regulates the activity of Ca2+-permeable NCC in hippocampal neurons and could potentially modulate key neuronal functions, including neurotransmission and neuronal excitability, via membrane depolarization.

Animals↗

PubMed1996

Modulation by polycationic Ca(2+)-sensing receptor agonists of nonselective cation channels in rat hippocampal neurons.

We recently cloned an extracellular calcium (Ca2+0)-sensing receptor (CaR) from bovine parathyroid. The CaR is also expressed in various regions of brain, suggesting that it could potentially mediate some of the well-known but poorly understood effects of Ca2+0 on neuronal function. We have now examined the effects of polycationic CaR agonists on the activity of nonselective cation channels (NCC) in cultured rat hippocampal neurons, using the cell-attached configuration of the patch clamp technique and applying CaR active agents to the external bath solution. The polycationic CaR agonist, neomycin (100 microM), as well as an elevated concentration of Ca2+0 (3 mM), which is known to activate the cloned CaR, significantly increased the probability of channel opening (Po). The polyamine, spermine (300 microM), which also mimics the actions of Ca2+0 on the cloned CaR, produced similar changes in Po in rat hippocampal neurons. Elevation of Ca2+0 also increased Po for a similar NCC in HEK293 cells transfected with the cloned human CaR but not in nontransfected HEK cells. Thus the CaR can regulate the activity of Ca(2+)-permeable NCC in hippocampal neurons and could potentially modulate key functions of these cells, including neurotransmission and neuronal excitability.

Animals↗

PubMed1985

Intermembrane linkage mediated by tubulin.

Two membranes from brain lipids were formed in the presence of brain tubulin and their electrical potentials were simultaneously measured. When electrical pulses were applied across one of them, displacements of the potential of the other membrane were found even when the membranes were not in contact. This effect was observed only in the presence of polymerized tubulin. It was not found in the presence of depolymerized tubulin or in other control experiments. The findings suggest that the microtubule fiber networks may serve as an interconnecting system between membranes or membrane bounded compartments.

Animals↗

PubMed1985

The role of cytoskeleton in the mechanisms of electric field effects and information transfer in cellular systems.

Microtubules and other cytoskeletal elements are ubiquitous components of all kinds of cellular systems. The suggestion is made that they are implicated in the mechanisms of biomedical and therapeutic field effects as well as in the processes of information transfer in neurons and other cells. Defined electrical properties and orientational field effects in microtubule systems are considered as a basis of such functions of the cytoskeleton. The concrete mechanisms of transfer of signals along the microtubules and other cytoskeletal fibres may involve cooperative periodical changes of conformation, of ion binding, or of different electrical parameters and enzymatic activities of their components.

Acupuncture Therapy↗