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Biomedical subjects

G Matthews

Publications and source records attributed to G Matthews.

At least 127 records · Page 7Linked to original sources
PubMed1984

Dark noise in the outer segment membrane current of green rod photoreceptors from toad retina.

The outer segment membrane current of single green rods from toad retina was recorded with a suction electrode, and the rate of spontaneous noise events similar to single-photon responses was measured at different temperatures. The activation energy, Gibbs free energy of activation, and entropy of activation for the process producing spontaneous events were similar to the values reported for thermal isomerization of free 11-cis-retinal (Hubbard, 1966), suggesting that thermal isomerization of the chromophore may be the trigger for the spontaneous events. The apparent rate constant for thermal activation of the green rod photopigment was about 4 times higher than in red rods but about 1000 times lower than for free 11-cis-retinal. Thus, both red and green rod opsin appear to stabilize 11-cis-retinal against thermal isomerization, but green rod opsin is somewhat less effective. The speed of the average dim-flash response increased as temperature was raised, as reported previously in both cone and rod photoreceptors. The reciprocal of the time-to-peak of the dim-flash response had an average Q10 of 3.3 between 20 and 30 degrees C. Changing temperature shifted the time scale of the response without altering response wave form, suggesting that all delay stages shaping the light response were approximately equally affected by temperature. At temperatures greater than 25 degrees C, flash responses were sometimes biphasic, i.e. inward dark current first decreased after a flash, then transiently increased beyond the resting dark level.

Animals↗
PubMed1984

Location and function of voltage-sensitive conductances in retinal rods of the salamander, Ambystoma tigrinum.

The functional role and spatial location of voltage-sensitive conductances that modify the light-evoked electrical signals were studied in retinal rods of the tiger salamander. An isolated rod was drawn into a suction electrode for recording membrane current and impaled with an intracellular electrode for recording membrane potential and passing current. A bright flash gave a rapid initial hyperpolarization that relaxed to a smaller plateau. Simultaneously the dark current of the outer segment was shut off with the time course of a rounded step function. This characteristic difference between the wave forms demonstrates that the voltage relaxation does not result from reopening of light-sensitive channels. The voltage relaxation in (2) did not require light or interruption of the dark current, as the wave form was duplicated by suddenly switching off a depolarizing current injected during steady saturating light. This is explained if the relaxation depends purely on voltage-sensitive conductances. The voltage response to a dim flash reached its peak value before the current response. The voltage wave form was predicted assuming that the recorded photo-current drove a linear high-pass filter with parameters derived from analysis of the voltage response to injection of a current step. When the intracellular voltage was changed by current injection the slope resistance of the outer segment slowly declined to a lower level, indicating that the outer segment contains a voltage-sensitive conductance. When a current step was injected in bright steady light, the current recorded from the outer segment consisted of a capacity component proportional to dV/dt and a small extracellular leakage current but no detectable ionic current. This supports other evidence indicating that light-sensitive channels comprise the main or exclusive ionic conductance of the outer segment. The behaviour in (5) is explained if the light-sensitive channels themselves are slowly opened by hyperpolarization and closed by depolarization. Analysis of the current-injection experiments suggests that most of the high-pass filtering in a rod results from the action of voltage-sensitive conductances located in the inner segment. Addition of 10 mM-CsCl to the Ringer solution abolished the relaxation in the voltage response to a bright flash but left intact the high-pass filtering of small signals. This would be explained by a selective block of one of two sets of voltage-sensitive channels in the inner segment or by a voltage-sensitive block of one kind of channel.

Ambystoma↗
PubMed1983

Temperature effects on the membrane current of retinal rods of the toad.

Thermal effects on the visual transduction mechanism of toad rods were examined by recording the membrane current of a single outer segment while changing the temperature within the range 15-30 degrees C. Warming increased the amplitude rmax of the saturating flash response. This effect had a Q10 of about 1.8 and may result from an increase in the light-sensitive conductance. The flash sensitivity decreased with increasing temperature, while the half-saturating flash intensity increased. There was no evidence of a temperature effect on the probability that an incident 500 nm photon triggered an electrical response. Together with the results in (2) and (3) this indicates that at higher temperature a successfully absorbed photon blocked a smaller fraction of the light-sensitive conductance. Upon warming, the time scale of the flash response shortened but the characteristic wave form was preserved. The speed of the dim flash response, measured by the reciprocal of its time-to-peak, had a Q10 of 2.7 and an apparent activation energy of 16.8 kcal mole-1. The power spectrum of the continuous component of the dark noise could be predicted at different temperatures by assuming that the underlying event was shaped by two of the four delays required to fit the light response. This behaviour is consistent with the notion that the continuous noise arises within the cascade of processes controlling the internal transmitter concentration of the outer segment.

Animals↗
PubMed1983

Physiological characteristics of single green rod photoreceptors from toad retina.

The outer segment membrane current of single isolated green and red rods from toad retina was recorded with a suction electrode, and characteristics of the response to light were examined. The maximum response amplitude of green rods was smaller than that of red rods, but the density of dark current along the green rod outer segment was similar to previously reported values for red rods. Thus, the smaller maximum response is explained by the shorter outer segment of green rods (45 vs. 60 microns). The intensity-response relation was fitted by a Michaelis equation with half-saturating photon density corresponding to about 55 isomerizations per flash. The form of the green rod light response was similar to that of red rods: in both cases the kinetics were consistent with four first-order delay stages shaping the light response. The time-to-peak of the dim-flash response was usually about 1 sec for both green and red rods in the present experiments. The spectral sensitivity curve of green rods was fitted by the nomogram for a vitamin A1-based pigment with lambda max = 433 nm. The relation between steady light intensity and flash sensitivity of green rods obeyed the Weber-Fechner relation, and the average background intensity necessary to reduce sensitivity to half of its dark level corresponded to about 4 isomerizations sec-1. This is slightly lower than the value of about 8 isomerizations sec-1 reported for toad red rods by Baylor, Matthews & Yau (1980). Green rods were similar to red rods in all respects except spectral sensitivity. Thus, no evidence was found to support the assertion that green rods are 'cone-like'.

Animals↗
PubMed1983

Relationship of antihypertensive effect of enalapril to serum MK-422 levels and angiotensin converting enzyme inhibition.

In hypertensive patients the time courses for the rise in serum MK-422 level, and fall in both angiotensin converting enzyme (ACE) activity and blood pressure after 10 mg of enalapril were very similar. A close relationship between serum MK-422 levels and percentage ACE inhibition could be demonstrated and the acute fall in blood pressure showed a good correlation with either measurement. With chronic administration, serum MK-422 levels increased linearly with the dose of enalapril. As in the acute study, close relationships between the serum MK-422 level and ACE inhibition, and between either measurement and the fall in blood pressure, could be demonstrated after chronic enalapril administration. However, when compared to the acute response, the ACE inhibition dose-response line was shifted to the right after chronic enalapril therapy suggesting that enalapril may lead to ACE induction in humans. This did not appear to influence significantly the blood pressure lowering effect of enalapril or the relationship between ACE inhibition and the hypotensive effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Decreased uterine bradykinin receptors during captopril infusion in rats.

To assess whether local tissue changes in bradykinin metabolism occur with captopril, the effect of intravenous infusion of bradykinin and captopril on bradykinin receptors in rat uterine smooth muscle was compared. Bradykinin and captopril decreased both the blood pressure and the number of bradykinin uterine receptors, estimated by direct radiolabeled binding techniques, without changing receptor affinity. These results demonstrate that bradykinin "down-regulates" its membrane receptor in rat myometrium. The similar change in receptor numbers induced by captopril could be explained by a local increase in bradykinin at receptor sites. The increase in local tissue level of bradykinin may contribute to the hypotensive action of captopril.

Animals↗
PubMed1982

Clinical freedom.

Explore the source record for details and available documents.

Choice Behavior↗
PubMed1980

Two components of electrical dark noise in toad retinal rod outer segments.

1. Physiological noise in the visual transduction mechanism was studied by recording membrane current from single rod outer segments in pieces of isolated toad retina. 2. The inward current in darkness showed spontaneous fluctuations which disappeared during the response to bright light. 3. The dark noise consisted of two components, a continuous fluctuation of rms amplitude about 0.2 pA and occasional discrete events about 1 pA in size. 4. Intervals between discrete events followed the exponential distribution expected of a Poisson process with a mean rate of about one event per 50 sec (20 degrees C). 5. The amplitude and power spectrum of the discrete events resembled those of single photon effects in the same rod, suggesting that discrete events may arise from spontaneous activation of single rhodopsin molecules. 6. The temperature dependence of the mean frequency of occurrence of discrete events gave an activation energy of 22 kcal mole-1, probably characteristic of thermal isomerization of rhodopsin. 7. The variance of the continuous component of the dark noise rose linearly with the length of the outer segment drawn into the suction electrode, indicating that this component is generated in the outer segment. 8. The power spectrum of a rod's continuous noise was usually fitted by the square of a Lorentzian with the same time constant as that of the four first-order delays in the cell's single photon response. The shot effects composing the continuous component thus appear to be shaped by two of four sequential processes in transduction. 9. The variance and spectrum of the continuous noise are interpreted to reflect shot effects about 1/400 the size of a single photon effect occurring at a frequency of 6 x 10(3) sec-1. 10. The rod's flash sensitivity was halved by a steady light to giving about 8 photoisomerizations sec-1. The much lower mean rate of discrete events indicates that Io in increment sensitivity experiments on individual receptors is not set by thermal activation of rhodopsin. 11. Values of sensitivity and time-to-peak flash response collected from many cells in darkness were correlated by the same power law relation obtaining in the presence of backgrounds. The correlation observed would be explained if a single variable controlled both the gain and time scale of several stages of the transduction mechanism in background light and in darkness.

Animals↗
PubMed1979

An objective measure of physical activity for epidemiologic research.

The development of a device is reported called the Large-scale integrated Motor Activity Monitor to examine physical activity during individuals' normal daily lives. The unit which is slightly larger than a wrist watch records body movement when worn at various body locations. Two population studies were conducted to evaluate the units. Experiment 1 examined 20 male graduate students for a two-day period. The data indicated that the units were sensitive to individual differences in physical activity and did not interfere with normal activities. Experiment 2 compared 10 Physical Education majors with 10 non-Physical Education majors by having individuals log activities and record movement counts for a two-day period. The movement data revealed that the monitors significantly discriminated between the two populations. The energy expenditure derived from the specific loggings was highly related (r = +.69) to the trunk movements, indicating that the movement counts are an accurate estimate of physical activity. The high relationship to energy analysis, the sensitivity of the units and the ease of implementation indicate that the units may be useful in relating normal activity to acute heart disease and to risk factors such as obesity and lipoproteins.

Energy Metabolism↗
PubMed1979

Glycine, GABA and synaptic inhibition of reticulospinal neurones of lamprey.

1. Intracellular recordings were made from the cell bodies and axons of giant reticulospinal neurones (Müller cells) of the lamprey and the effects of a variety of putative neurotransmitters tested. Bath-applied acetylcholine, carbamylcholine, norepinephrine, dopamine, histamine and serotonin were without effect. Glycine and gamma-aminobutyric acid (GABA) hyperpolarized and reduced the input resistance of cell bodies but had no effect on the membrane conductance of axons. 2. The threshold dose of bath-applied GABA or glycine for a conductance change in somata was about 0.5 mM and the maximum effect was reached at about 10 mM. The maximum conductance change produced by glycine was always greater than that produced by GABA. 3. Replacement of the sodium in the bathing saline with lithium or choline prolonged the conductance change produced by ionophoretically applied glycine or GABA, suggesting the presence of sodium-dependent uptake systems for glycine and GABA. 4. The reversal potentials for responses to ionophoretically applied glycine and GABA average about --83 mV, the same as that for the inhibitory post-synaptic potential (i.p.s.p.) produced in Müller cells by stimulation of the ipsilateral vestibular nerve. 5. The i.p.s.p. and drug responses appeared to involve an increase in chloride conductance, since their reversal potentials were shifted appropriately by changes in either internal or external chloride. 6. Changes in extracellular potassium concentration also changed i.p.s.p. and drug reversal potentials. However, these effects could be attributed to secondary changes in internal chloride. 7. The receptors for GABA and glycine appeared to be different because of the absence of cross-desensitization and because, at doses below 20 microM, picrotoxin and bicuculline selectively blocked GABA responses while strychnine selectively blocked glycine responses. 8. At concentrations of 20 microM, strychnine eliminated the i.p.s.p. while picrotoxin and bicuculline had no effect. Further, the i.p.s.p. and glycine response of Müller cells located in the isthmic region of the midbrain had the same threshold sensitivity to strychnine. However, the glycine response of other Müller cells was more sensitive to strychnine than was the i.p.s.p. 9. We conclude that glycine is a better candidate for the inhibitory transmitter onto Müller cells than is GABA.

Animals↗
PubMed1979

Glutamate and synaptic excitation of reticulospinal neurones of lamprey.

1. Intracellular recordings were made from the cell bodies and axons of giant reticulospinal neurones (Müller cells) of the lamprey, and responses to bath- and ionophoretically applied glutamate and aspartate were studied. 2. Bath-applied glutamate and aspartate depolarized both cell bodies and axons, but there appeared to be an associated conductance increase only in the cell bodies. The depolarization of Müller axons by the bath-applied drugs probably resulted from the passive flow of current into them from spinal cells to which the axons are coupled electrically. 3. The reversal potentials for responses to ionophoretically applied glutamate and for excitatory post-synaptic potentials (e.p.s.p.s) evoked by stimulation of the contralateral vestibular nerve were directly determined in Müller cell bodies which had been damaged by penetration with low-resistance electrodes. The glutamate and e.p.s.p. reversal potentials were identical, the average difference in eight cells being 0.31 mV. The absolute value of the e.p.s.p.--glutamate reversal potential varied from --16 to --35 mV in different cells, with the more negative values occurring in less damaged cells with higher resting potentials. 4. Injection of Cl into Müller cell bodies had no effect on the e.p.s.p.--glutamate reversal potential. Reduction of the extracellular Na concentration to 1 over 10 normal produced a negative shift in the glutamate reversal potential. 5. It is proposed that the natural excitatory transmitter and glutamate produce identical conductance changes in Müller cells, involving an increase in Na and K conductance.

Animals↗
PubMed1978

A simplified polyacrylamide gel electrophoresis apparatus for simultaneous application of multiple buffer systems or detergent combinations.

A previous design of an apparatus for the simultaneous fractionation by polyacrylamide gel electrophoresis in 10 different buffer systems (1) was replaced by a greatly simplified new design, employing small, cylindrical buffer partitions within the lower buffer reservoir and/or upper buffer reservoir of a conventional, temperature-regulated polyacrylamide gel electrophoresis apparatus for cylindrical gels. The apparatus was tested in application to the problem of simultaneous polyacrylamide gel electrophoresis in different buffer systems with the purpose of optimizing the operative pH for a particular fractionation problem. It was also applied to fractionations in a single buffer system to which various combinations of ionic and nonionic detergents were admixed.

Adenylyl Cyclases↗
PubMed1978

REM sleep in primary depression: a computerized analysis.

REM sleep in 35 inpatients with primary depression was automatically analyzed for 7 consecutive nights during placebo administration. For the total night of sleep, as well as each individual REM period, the number of REMs, their total voltage integral over time, the sum of their durations and the average REM size were automatically calculated. Validity of these automated REM measures was established by significant correlations with manually scored REM measures. Changes in REM sleep across the night were also investigated. Similar to findings in normal subjects, REM time did not change from REM period to REM period. Average REM size increased significantly from REM period 2-3 and 3-4. Contrary to what is seen in normal subjects, REM frequency was high during the first REM period, significantly decreased from the first to second REM period and then remained constant. Finally, a significant inverse correlation between REM frequency for the first REM period and REM latency was noted. This pattern of REM sleep is interpreted as indicating a high pressure for phasic REM at the beginning of the night which is dissipated by the first REM period.

Adult↗