Search PubMed⌕ Search

Biomedical subjects

D S Koh

Publications and source records attributed to D S Koh.

27 records · Page 2Linked to original sources
PubMed1995

Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS.

Recording of glutamate-activated currents in membrane patches was combined with RT-PCR-mediated AMPA receptor (AMPAR) subunit mRNA analysis in single identified cells of rat brain slices. Analysis of AMPARs in principal neurons and interneurons of hippocampus and neocortex and in auditory relay neurons and Bergmann glial cells indicates that the GluR-B subunit in its flip version determines formation of receptors with relatively slow gating, whereas the GluR-D subunit promotes assembly of more rapidly gated receptors. The relation between Ca2+ permeability of AMPAR channels and the relative GluR-B mRNA abundance is consistent with the dominance of this subunit in determining the Ca2+ permeability of native receptors. The results suggest that differential expression of GluR-B and GluR-D subunit genes, as well as splicing and editing of their mRNAs, account for the differences in gating and Ca2+ permeability of native AMPAR channels.

Animals↗
PubMed1994

Na(+)-activated K+ channels localized in the nodal region of myelinated axons of Xenopus.

1. A potassium channel activated by internal Na+ ions (K+Na channel) was identified in peripheral myelinated axons of Xenopus laevis using the cell-attached and excised configurations of the patch clamp technique. 2. The single-channel conductance for the main open state was 88 pS with [K+]o = 105 mM and pS with [K+]o = 2.5 mM ([K+]i = 105 mM). The channel was selectively permeable to K+ over Na+ ions. A characteristic feature of the K+Na channel was the frequent occurrence of subconductance states. 3. The open probability of the channel was strongly dependent on the concentration of Na+ ions at the inner side of the membrane. The half-maximal activating Na+ concentration and the Hill coefficient were 33 mM and 2.9, respectively. The open probability of the channel showed only weak potential dependence. 4. The K+Na channel was relatively insensitive to external tetraethylammonium (TEA+) in comparison with voltage-dependent axonal K+ channels; the half-maximal inhibitory concentration (IC50) was 21.3 mM (at -90 mV). In contrast, the channel was blocked by low concentrations of external Ba2+ and Cs+ ions, with IC50 values of 0.7 and 1.1 mM, respectively (at -90 mV). The block by Ba2+ and Cs+ was more pronounced at negative than at positive membrane potentials. 5. A comparison of the number of K+Na channels in nodal and paranodal patches from the same axon revealed that the channel density was about 10-fold higher at the node of Ranvier than at the paranode. Moreover, a correlation between the number of K+Na channels and voltage-dependent Na+ channels in the same patches was found, suggesting co-localization of both channel types. 6. As weakly potential-dependent ('leakage') channels, axonal K+Na channels may be involved in setting the resting potential of vertebrate axons. Simulations of Na+ ion diffusion suggest two possible mechanisms of activation of K+Na channels: the local increase of Na+ concentration in a cluster of Na+ channels during a single action potential or the accumulation in the intracellular axonal compartment during a train of action potentials.

Animals↗
PubMed1994

Activating effect of the flavonoid phloretin on Ca(2+)-activated K+ channels in myelinated nerve fibers of Xenopus laevis [corrected].

The effects of the flavonoid phloretin on K+ channels in amphibian myelinated nerve were studied by patch clamping. The open probability of Ca(2+)-activated K+ channels was greatly increased by external phloretin (10-200 microM) due to a shift of the membrane potential for half-maximal activation, E50, of -63.9 mV (80 microM phloretin). Open times were prolonged and closed times shortened. Channel activation by phloretin developed slowly (tau on = 33.4 s) and its washout was even slower (tau off,1 = 4.7 and tau off,2 = 183.2 s). In contrast, submillimolar phloretin blocked two delayed rectifier K+ channels (I and F) whereas the gating of the ATP-sensitive and the flickering K+ channel were unaffected. Phloretin may directly affect the voltage sensor of K+ channels.

Adenosine Triphosphate↗
PubMed1993

A method for rapid exchange of solutions at membrane patches using a 10-microliters microcapsule.

A rapid exchange (less than 2 ms) of the bath solution facing a membrane patch is accomplished by driving the tip of a pipette from the bath through a 100-microns oil layer into a small capsule filled with 10 microliters test solution. The microcapsule method can be applied to both excised patch configurations, inside-out and outside-out patches. On and off reactions of Ca(2+)-activated K+ channel activity have been recorded after changing the intracellular Ca2+ concentration using an inside-out patch. A blockade of these K+ channels by external tetraethylammonium ions is demonstrated with an outside-out patch. The blocking kinetics of delayed-rectifier K+ channels by a purified peptide toxin from snake venom, dendrotoxin, could be measured with our microcapsule method. Using tiny volumes of test solutions this method can be helpful in experiments involving scarce or expensive solutions.

Animals↗
PubMed1992

A TEA-insensitive flickering potassium channel active around the resting potential in myelinated nerve.

A novel potassium-selective channel which is active at membrane potentials between -100 mV and +40 mV has been identified in peripheral myelinated axons of Xenopus laevis using the patch-clamp technique. At negative potentials with 105 mM-K on both sides of the membrane, the channel at 1 kHz resolution showed a series of brief openings and closings interrupted by longer closings, resulting in a flickery bursting activity. Measurements with resolution up to 10 kHz revealed a single-channel conductance of 49 pS with 105 mM-K and 17 pS with 2.5 mM-K on the outer side of the membrane. The channel was selective for K ions over Na ions (PNa/PK = 0.033). The probability of being within a burst in outside-out patches varied from patch to patch (> 0.2, but often > 0.9), and was independent of membrane potential. Open-time histograms were satisfactorily described with a single exponential (tau o = 0.09 msec), closed times with the sum of three exponentials (tau c = 0.13, 5.9, and 36.6 msec). Sensitivity to external tetraethylammonium was comparatively low (IC50 = 19.0 mM). External Cs ions reduced the apparent unitary conductance for inward currents at Em = -90 mV (IC50 = 1.1 mM). Ba and, more potently, Zn ions lowered not only the apparent single-channel conductance but also open probability. The local anesthetic bupivacaine with high potency reduced probability of being within a burst (IC50 = 165 nM). The flickering K channel is clearly different from the other five types of K channels identified so far in the same preparation. We suggest that this channel may form the molecular basis of the resting potential in vertebrate myelinated axons.

Animals↗
PubMed1991

ATP-sensitive and Ca-activated K channels in vertebrate axons: novel links between metabolism and excitability.

Two types of metabolically regulated K channels have been identified for the first time in enzymatically demyelinated fibres of amphibian sciatic nerve using the patch-clamp technique. A maxi K channel with a single-channel conductance of 132 pS (105 mM K on both sides of the membrane, 15 degrees C) is activated both by micromolar concentrations of internal Ca and by depolarization. A second type of K channel with a conductance of 44 pS is inhibited by intracellular adenosine 5'-triphosphate (ATP) with a half-maximal inhibitory concentration (IC50) of 35 microM. It is blocked by submicromolar concentrations of external glibenclamide. Both channels are sensitive to external tetraethylammonium chloride (IC50 = 0.2 mM for the maxi K channel and 4.2 mM for the ATP-sensitive channel). They may be part of a complex feedback system regulating axonal excitability under various metabolic conditions.

Action Potentials↗
PubMed1981

Micronema in man: third fatal infection.

Micronema, normally free-living in soil and humus, rarely invades and reproduces in the central nervous system, kidneys, lungs, maxillae and nasal cavity of equines. Two Micronema infections causing fatal meningoencephalomyelitis in man have been reported from Canada and Texas. Here we report a third infection in a 54-year-old black man, resident of Washington, D.C., who probably acquired the infection from decubitus ulcers. The worms in this patient were in the liver, heart and brain. The Micronema species was not identified.

Brain↗
PubMed1966

Scaling of musical preferences by the mentally retarded.

The ability of institutionalized retardates in scaling musical preferences was compared with that of normals. The retardates' scale values and scale forms obtained by two kinds of scaling procedures are very similar to those of normals. Deficits, however, are observed in their lower internal consistency and relative uncertainty and in higher response polarization and perseveration.

Adult↗