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Biomedical subjects

K Chinn

Publications and source records attributed to K Chinn.

13 recordsLinked to original sources

Tympanometry and otoscopy prior to myringotomy: issues in diagnosis of otitis media.

Tympanometry and pneumatic otoscopy were compared to findings at myringotomy in 86 children (163 ears). Seventy percent of the ears (115) had effusion, as revealed by myringotomy. Sensitivity and specificity for tympanometry were 90% and 86%, respectively. Sensitivity and specificity for pneumatic otoscopy were 93% and 58%, respectively. A chi-square was performed to compare the sensitivity and specificity to tympanometry to otoscopy, revealing tympanometry significantly better at determining non-effusion states. Additionally, a combined otoscopy and tympanometry sensitivity and specificity were calculated for those otoscopy and tympanometry determinations in agreement, revealing both sensitivity and specificity above 90%. A Fisher's exact probability test revealed no significant differences for the accuracy of tympanometry over otoscopy when the determinations of each were not in agreement. Implications of these results are discussed.

Acoustic Impedance Tests

Contribution of delayed rectifier and inward rectifier to repolarization of the action potential: pharmacologic separation.

Outward potassium (K) currents contribute to the repolarization process of cardiac action potentials. There are, however, multiple K currents. Recently, two putatively specific K channel blockers have been developed as potential class III antiarrhythmic agents. E-4031 appears to block specifically a fast component of the delayed rectifier (IK), and RP 58866 is a reported inward rectifier current (IK1) blocker. In the present experiments, we examined the effects of E-4031 and RP 58866 on action potentials recorded from guinea pig papillary muscles to determine whether the properties of IK and IK1 measured in whole-cell experiments would be manifested in distinct effects. Both compounds prolonged the APD50 (action potential duration at 50% repolarization) and APD90 (action potential duration at 90% repolarization). However, RP 58866 did not significantly prolong the action potential at voltages of 0 mV and above, while E-4031 did. The results suggest that preferential IK1 block results in a change in action potential waveform that is distinct from that resulting from block of other outward K currents. This could thus be used as a simple first-pass screening tool in determining a preliminary mechanism of action of class III antiarrhythmics prior to more time-consuming but necessary whole-cell voltage clamp experiments.

Action Potentials

Interconversions of lipid aggregates in rat and model bile.

The dynamic interchange of cholesterol and the phase transition between nonmicellar and micellar aggregates in rat and model bile were characterized with gel-permeation chromatography, quasi-elastic light scattering, turbidity measurements, and by radiolabeling lipid aggregates in bile. Cholesterol partitioned into either the micellar or nonmicellar phases independent of the lipid aggregate structure. In model bile, increasing bile salt concentrations led to a decrease in the relative proportion of nonmicellar aggregates beginning at 5 mM taurocholate (TC), while the relative cholesterol content of the nonmicellar fraction increased from 1.0 to 2.7 +/- 2.0 (means +/- SD). In rats, creation of a biliary fistula resulted in a decrease of bile salts from 41 to 4 mM. Mixed micelles increased from 25 to 120 A in radius, while nonmicellar aggregates increased from 180 to 800 A in radius. Addition of TC to model bile (cholesterol:lecithin = 1:1) vesicles with total lipid concentrations less than 7 mM yielded a progressive shift of vesicles (450 A) to mixed micelles (30 A). For mixtures with higher total lipid concentrations, addition of TC promoted substantial vesicle aggregation and resulted in formation of a third phase containing lipid aggregates larger in size than the initial vesicles. These results suggest that rapid exchange of cholesterol occurs in bile and that significant remodeling of vesicles can occur. These alterations in vesicles include both enrichment in cholesterol content and formation of larger aggregates during increases in bile salt concentration.

1,2-Dipalmitoylphosphatidylcholine

Pinacidil opens ATP-dependent K+ channels in cardiac myocytes in an ATP- and temperature-dependent manner.

Pinacidil is an antihypertensive agent that has been found to increase potassium conductance. This study examined the type of K channel affected by pinacidil in cardiac myocytes. Pinacidil shortened the action potential duration in papillary muscle. The effect was reversible upon addition of glyburide, a known IKATP blocker. The effect of pinacidil was temperature-dependent. Action potential duration was shortened more rapidly and to a greater extent at 37 degrees C than at 23 degrees C. Whole-cell experiments showed that I-V curves lost rectification after pinacidil treatment. As with the action potential experiments, the effect was more rapid at 37 degrees C than at 23 degrees C. Rectification was restored after exposure to glyburide. The I-V curve generated after pinacidil exposure was similar to that observed by others after treatment with metabolic inhibitors that activate IKATP. The effect of pinacidil was also ATP-dependent. Addition of 5 mM ATP to the internal solution prevented activation of IKATP. These data indicate that pinacidil activates IKATP.

Action Potentials

Temperature-dependent subconducting states and kinetics of deltamethrin-modified sodium channels of neuroblastoma cells.

The effects of temperature on the properties of sodium channels from mouse neuroblastoma cells modified by the pyrethroid insecticide deltamethrin were investigated using the patch-clamp technique. The study was aimed at determining various states of modified channels which were expected to be revealed by raising the temperature as a result of an increase in channel activity. After exposure to 10 microM deltamethrin, the decay of whole cell sodium current at -30 mV was drastically slowed. It is expressed by two exponential functions at 11 degrees C and by three exponential functions at room temperature (22 +/- 1 degree C). Thus, raising the temperature reveals a new process. Whole cell sodium tail currents associated with step repolarization from -30 mV to -100 mV were best fit by the sum of two exponential functions both at 11 degrees C and at room temperature. The decay of the summed modified single sodium channel currents at -30 mV was expressed by a single exponential function at 11 degrees C, and by two exponential functions at room temperature. In keeping with these results, the open time histograms show the single (11 degrees C) and double (room temperature) exponential distributions. Thus, raising the temperature allows a new single channel process to be revealed. Other modified open states observed previously at 11 degrees C were also found at room temperature including a flickering state and a subconducting state. In addition, several new subconducting states were found at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ion channels activated by light in Limulus ventral photoreceptors.

The light-activated conductance of Limulus ventral photoreceptors was studied using the patch-clamp technique. Channels (40 pS) were observed whose probability of opening was greatly increased by light. In some cells the latency of channel activation was nearly the same as that of the macroscopic response, while in other cells the channel latency was much greater. Like the macroscopic conductance, channel activity was reduced by light adaptation but enhanced by the intracellular injection of the calcium chelator EGTA. The latter observation indicates that channel activation was not a secondary result of the light-induced rise in intracellular calcium. A two-microelectrode voltage-clamp method was used to measure the voltage dependence of the light-activated macroscopic conductance. It was found that this conductance is constant over a wide voltage range more negative than zero, but it increases markedly at positive voltages. The single channel currents measured over this same voltage range show that the single channel conductance is independent of voltage, but that channel gating properties are dependent on voltage. Both the mean channel open time and the opening rate increase at positive voltages. These properties change in a manner consistent with the voltage dependence of the macroscopic conductance. The broad range of similarities between the macroscopic and single channel currents supports the conclusion that the 40-pS channel that we have observed is the principal channel underlying the response to light in these photoreceptors.

Adaptation, Physiological

Stabilization of sodium channel states by deltamethrin in mouse neuroblastoma cells.

The effect of the pyrethroid insecticide deltamethrin on sodium channels of mouse neuroblastoma cells was investigated using the patch-clamp technique. The study was aimed at determining how the effects of deltamethrin at the whole cell level would be reflected in the modified properties of single sodium channel currents. Whole cell recording showed that deltamethrin prolonged sodium currents in neuroblastoma cells by several orders of magnitude. Single channel recordings showed that a variety of channel states were prolonged by deltamethrin. Not only was the open state prolonged by several orders of magnitude but a closed or inactivated state was also prolonged, leading to less frequent channel openings. A subconducting state and a flickering state were observed in the presence of deltamethrin as well as a state in which channels opened with some delay after the termination of a depolarizing pulse. The results are compatible with the hypothesis that deltamethrin stabilizes a variety of channel states by reducing the transition rates between them. This allows states that are normally very brief to be detected more easily.

Action Potentials

Light-evoked depolarizations in the retina of Strombus: role of calcium and other divalent cations.

Previous studies indicate that overlapping inward sodium and outward potassium currents play a role in generating the waveform of light-evoked depolarizations (LEDs) in one type of retinal neuron in Strombus luhuanus, a marine gastropod [Chinn, K. S., and Gillary, H. L. (1985). Comp. Biochem. Physiol. 80A:233-245]. This paper concerns the effects of divalent cations on the LED. The LED can exhibit a distinct early phase of depolarization (DE). Increasing the [Ca2+] in the artificial seawater (ASW) bathing medium reduced the amplitude of the entire LED, and omitting Ca2+ increased it. Adding 10 mM Sr2+ or 10 mM Mn2+ to either normal ASW or 0-Ca2+ ASW decreased the LED amplitude. Adding 10 mM Ba2+ to 0-Ca2+ ASW also decreased the LED amplitude, but adding Ba2+ to normal ASW selectively increased DE. Cd2+ (100 microM) selectively reduced DE when added to normal ASW but not when added to 0-Ca2+ ASW. The results show that a variety of divalent cations can alter the currents that underlie the LED. They also suggest that an inward Ca2+ current occurs during DE.

Animals

The effect of nucleotides on the rate of spontaneous quantum bumps in Limulus ventral photoreceptors.

The effect of intracellular nucleotides on the rate of spontaneous quantum bumps in Limulus ventral photoreceptors has been examined. Internal dialysis of photoreceptors with solutions lacking nucleotide leads to an elevation of the quantum bump rate that can be reversed by introduction of nucleotide. Similarly, elevation occurs after treating intact cells with the metabolic inhibitor 2-deoxyglucose. This effect can be reversed by intracellular injection of ATP. The rate of spontaneous quantum bumps in unpoisoned cells can be reduced to below normal levels by injection of ATP. These results support the hypothesis that high-energy nucleotides suppress the rate of spontaneous quantum bumps.

Alkaline Phosphatase

Calcium mediates the light-induced decrease in maintained K+ current in Limulus ventral photoreceptors.

In addition to increasing the conductance to sodium, light reduces the maintained voltage-dependent potassium current (iK) in Limulus ventral photoreceptors. We have investigated the mechanism underlying this long-lasting decrease in ik. Intracellular injection of calcium produced a similar reduction of the voltage-dependent outward current. This reduction was not due to an activation of the voltage-dependent inward current (iin) because calcium injection reduced the outward current even under conditions where iin was blocked with Ni2+, and because calcium injection produced a decrease in conductance, as measured from the slope of the instantaneous i-V curve. The effect of light on ik could be blocked by injection of the calcium buffer EGTA (pCa 7.1) to an intracellular concentration of 50-70 mM. Even larger injections of the pH buffer MOPS (100-200 mM) did not reduce the effect of light on ik. These experiments show that intracellular free calcium (Cai2+) can reduce ik. Furthermore, since Cai2+ is known to increase in light, our results are consistent with the hypothesis that calcium is the internal transmitter for the light-induced decrease in ik.

Animals

Light reduces the voltage-dependent inward current in Limulus ventral photoreceptors.

In Limulus ventral photoreceptors, illumination not only increases a specialized light-activated sodium conductance but also modulates voltage-dependent conductances. Previous work has demonstrated that the delayed rectifier current is reduced by light; we report here that the early voltage-dependent inward current is also reduced by light. Furthermore, by maintained during continuous depolarization and that this maintained inward current can be reduced by light. EGTA injection was found to increase the maintained inward current.

Animals

Distinct lobes of Limulus ventral photoreceptors. I. Functional and anatomical properties of lobes revealed by removal of glial cells.

Removing the glial cells that encase Limulus ventral photoreceptors allows direct observation of the cell surface. Light microscopy of denuded photoreceptors reveals a subdivision of the cell body into lobes. Often one lobe, but sometimes several, is relatively clear and translucent (the R lobes). The lobe adjacent to the axon (the A lobe) has a textured appearance. Scanning electron microscopy shows that microvilli cover the surface of R lobes and are absent from the surface of A lobes. When a dim spot of light is incident on the R lobe, the probability of evoking a single photon response is two to three orders of magnitude higher than when the same spot is incident on the A lobe. We conclude that the sensitivity of the cell to light is principally a function of the R lobe.

Adaptation, Ocular