[Luminance and color contrast evoked pattern electroretinograms and visual evoked potentials].
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Biomedical subjects
Publications and source records attributed to M Korth.
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Pattern electroretinograms to onset-offset stimuli were studied in response to luminance-contrast (e.g. red-black or green-black) and color-contrast (e.g. red-green) stripe patterns of equal luminance. Onset responses to color-contrast patterns show no spatial selectivity and a constant peak latency at all spatial frequencies, a behavior different from that of luminance-contrast evoked responses (spatial selectivity and increasing peak latency with spatial frequency). These results are tentatively related to the physiology of tonic and phasic primate retinal ganglion cells and to the spatially selective and non-selective human contrast sensitivity to respectively luminance-contrast and color-contrast gratings.
The pattern-evoked electroretinogram (PERG) was studied in response to square-wave stripe patterns contrasting either between dark and colored stripes ("red-black" or "green-black" luminance contrast pattern) or between the two colors (red-green chromatic contrast pattern). All lights were matched in photopic luminance. A two-channel Maxwellian view system was used to present the stimuli in the onset-offset mode. When no pattern was present a mixture of both colors was seen. Different spatial frequencies were studied and the amplitudes of the onset response were evaluated. When the two luminance contrast patterns were presented, the responses showed a spatial selectivity. However the combination of the two colors (red-green contrast) resulted in a monotonic decrease of the response with spatial frequency. The spatially selective behavior of the response to luminance contrast patterns could be associated with the on-off center-surround organization of retinal receptive fields. The behavior of the response to chromatic-contrast patterns, on the other hand, could be explained by the action of color-opponent center-surround receptive fields as described in the primate.
The inotropic potencies of 8-substituted cyclic AMP analogues, applied as sodium salts and in form of benzyl esters, were determined in isolated guinea-pig papillary muscles contracting isometrically at a frequency of 0.2 Hz. Half-maximally effective concentrations, EC50, for the positive inotropic effect of 8-substituted cyclic AMP (sodium salt) increased in the order 8-(4-chloro-phenyl)thio-cyclic AMP, 8-tertiary-butyl-thio-cyclic AMP, 8-benzyl-seleno-cyclic AMP, 8-benzyl-thio-cyclic AMP, 8-methyl-thio-cyclic AMP, 8-bromo-cyclic AMP. Neutralization of the phosphate hydroxyl residue of 8-substituted cyclic AMP by a benzyl group yielded cyclic AMP benzyl esters (cAMP-O-Bn) which were 30 to 100 times more potent than the respective cyclic AMP salts. Cyclic AMP derivatives with a 8-(4-chloro-phenyl)thio- or a 8-tertiary butyl-thio substituent showed comparatively high inotropic potencies. The intrinsic activity was uniformely the same for all 8-substituted cyclic AMP derivatives and equalled that of isoprenaline. As measured by octanol/water partitioning (log P), the increase in lipophilicity of 8-substituted cyclic AMP by esterification with a benzyl group was 7000-fold for 8-bromo-cyclic AMP, 5000-fold for 8-methyl-thio-cyclic AMP, and approximately 1000-fold for the other derivatives. Within the series of benzyl esters, differences in lipophilicity were small. The positive inotropic effect of 8-substituted cyclic AMP analogues was accompanied by a shortening of contraction duration, mainly due to an abbreviation of relaxation time.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of phosphodiesterase inhibitors and of carbachol on the positive inotropic effect of 8-substituted cyclic AMP analogues was studied on isometrically contracting guinea-pig papillary muscles driven at a rate of 0.2 Hz. In muscles from reserpine-pretreated animals, the phosphodiesterase inhibitors 3-isobutyl, 1-methyl xanthine (IBMX; 20 mumol/l) and papaverine (10 mumol/l) shifted the concentration-effect curves of 8-substituted cyclic AMP benzyl esters to the left, decreasing the EC50 by a factor of 10 to 25. In the presence of IBMX (5 and 20 mumol/l) or papaverine (10 mumol/l), the slopes of the concentration-effect curves of 8-substituted cyclic AMP benzyl esters became flatter. The positive inotropic effect and the increase in Vmax, overshoot and duration of slow action potentials induced by cyclic AMP analogues were not affected by carbachol (0.1-10 mumol/l). In the presence of IBMX (20 mumol/l), however, carbachol (3 mumol/l) antagonized the positive inotropic effect of 8-substituted cyclic AMP derivatives, shifting the EC50-values by a factor of 3 to the right. Cyclic AMP content determined by radioimmunoassay in individual papillary muscles was raised 1.22 and 1.63-fold in the presence of 3 and 20 mumol/l IBMX. Isoprenaline (0.1 mumol/l) induced an increase in cyclic AMP content which was not significantly different from that produced by 20 mumol/l IBMX, but in contrast to the phosphodiesterase inhibitor enhanced force of contraction by 17.7 mN as compared to 1.5 mN obtained with 20 mumol/l IBMX. The findings are consistent with a model that describes the interaction between IBMX and cyclic AMP analogues as an additive effect with only endogenously accumulated cyclic AMP (due to phosphodiesterase inhibition) being involved in the negative inotropic effect of carbachol. From the failure of carbachol to affect the positive inotropic effect of cyclic AMP analogues, it is concluded, that cyclic AMP derivatives do not act as phosphodiesterase inhibitors, and that the well-known negative inotropic effect of carbachol in the presence of cyclic AMP-elevating drugs does not occur at a step beyond cyclic AMP accumulation.
Electric responses were recorded in the eyes of two normal subjects in response to a checkerboard pattern moving one square backwards and forwards (2 deg 44') at speeds varying between 13.5 and 2700 deg/s. The recorded waveforms suggest that a low-speed range (up to 250 deg/s) associated with increasing low-frequency response components can be distinguished from a high-speed range accompanied by increasing high-frequency wavelets. The range of velocities used is compared with target speeds employed in previous psychophysical and retinal single-unit recordings.
The pattern-evoked electroretinogram (PERG) was studied in three normal subjects under different levels of adaptation using pattern onset-offset stimulation. The occurrence of a response maximum (spatial selectivity) in the onset response at a certain spatial frequency can be interpreted as reflecting the activity of neurons having antagonistic center-surround receptive fields and allows an estimation of receptive-field center sizes. The present data suggest that in the light-adapted state, the majority of receptive fields, dominating the response can be estimated to have center diameters of 6-13 min of arc. With increasing dark adaptation, the spatial selectivity shifts from high to low spatial frequencies over 1.3-2.4 octaves, indicating that large receptive fields are active in the dark and small fields in the light. The physiological mechanisms of these changes are discussed on the basis of findings obtained from single-unit studies.
Electrooculography allows to measure the fundocorneal potential, a standing potential of the eye, under the conditions of light and dark adaptation. The results are expressed as the so-called Arden ratio. As was demon-strated by others in healthy volunteers, the Arden ratio, on the average, de-creases under Lithium treatment. However, in individual cases it can also remain unchanged or even rise. We have performed electrooculographic and adaptometric examinations in ten patients with affective disorders (DSM-III, 296. XX) and schizoaffective psychoses (DSM-III, 295.70). The criteria for the assignment of patients to lithium treatment were derived from a study by Angst. Arden ratios were determined six times, respectively, before lithium application and after a therapeutic lithium serum level (0.6-0.8 mmol/l) had been reached (cf. 5). The values observed during lithium treatment were significantly lower than those measured before lithium application. Dark adaptation, as measured using an adaptometer according to Goldmann-Weekers, was disturbed under lithium. The potential predictor function of these findings with regard to the lithium response is being investigated by means of a prospective study.
The concentration-dependence of the negative and positive inotropic effect of choline esters and of oxotremorine was studied in isometrically contracting papillary muscles of the guinea-pig. The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (IBMX, 100 mumol l-1), choline esters and oxotremorine produced concentration-dependent negative inotropic effects. Oxotremorine exhibited the highest negative inotropic potency (with a half-maximal effective concentration, EC50, of 20 nmol l-1) followed by carbachol (139 nmol l-1), methacholine (490 nmol l-1), acetylcholine in the presence of 10 mumol l-1 physostigmine (1.36 mumol l-1) and bethanechol (10 mumol l-1). Atropine was a competitive antagonist of the negative inotropic effects. Carbachol and oxotremorine decreased Vmax, overshoot and duration of slow Ca2+-dependent action potentials which had been elicited in the presence of 100 mumol l-1 IBMX. Choline esters produced a concentration-dependent positive inotropic effect. With an EC50 of 32 mumol l-1, carbachol was the most potent compound, followed by methacholine (35 mumol l-1), acetylcholine in the presence of 10 mumol l-1 physostigmine (46 mumol l-1) and bethanechol (142 mumol l-1). Compared to carbachol and methacholine which increased force by 100% of control, the increase induced by acetylcholine and bethanechol was only 64 and 58%, respectively. Atropine shifted the concentration-effect curves of all choline esters to higher concentrations. Choline esters caused intracellular Na+ activity to increase in the quiescent papillary muscle. This effect was reversed by atropine. Oxotremorine produced a small concentration-dependent positive inotropic effect (about 30% of the maximal effect of carbachol) which was resistant to atropine. Oxotremorine was a potent inhibitor of the positive inotropic effect of choline esters, and did not cause an increase in intracellular Na+ activity in the quiescent papillary muscle. The results show that muscarinic receptors of the ventricular myocardium mediate two inotropic effects, which are opposite in direction and differ in their concentration-dependence by a factor of 100. Although agonists differentiate between both inotropic effects, it is unknown whether the receptors involved represent receptor states or separate receptor subpopulations. The negative inotropic effect of choline esters and of oxotremorine can be best explained by adenylate cyclase inhibition. While stimulation of phosphoinositide hydrolysis might have been responsible for the positive inotropic effect of choline esters via modulation of cation-fluxes across the cell membrane, such a mechanism was not involved in the positive inotropic effect of oxotremorine.
The effect of the beta-adrenoceptor agonist, isoproterenol, on cytosolic calcium concentration ([Ca2+]i) was studied with the Ca2+-sensitive fluorescent indicator quin 2 in enzymatically dissociated rat ventricular myocytes. Under conditions in which cells have normal polarized resting membrane potential, isoproterenol (1 microM) produced a decrease in [Ca2+]i. In contrast, in the depolarized cells (by raising extracellular K+ concentration to 50 mM), isoproterenol (1 microM) caused an increase in [Ca2+]i. This isoproterenol-induced increase in [Ca2+]i in depolarized cells could be reversed by prior exposure of the cells to the Ca2+ channel blocker, verapamil (5 microM). The results indicate that isoproterenol can either decrease or increase [Ca2+]i depending on membrane potential. The actual effect of isoproterenol on [Ca2+]i at any given membrane potential probably reflects the relative contributions of isoproterenol-induced stimulation of Ca2+ buffering or effluxing activities (which favor a decrease in [Ca2+]i) and enhancement of Ca2+ influx through voltage-sensitive Ca2+ channels (which favors an increase in [Ca2+]i).
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The spatial selectivity of the electroretinogram in response to pattern onset-offset stimuli was studied in man at several levels of adaptation ranging from scotopic to photopic levels. Under conditions of rod function the peak of the spatial selectivity based on amplitude measurements of the pattern-onset response occurs at a low spatial frequency. With increasing light adaptation a gradual shift of the selectivity to higher spatial frequencies occurs. This change in the character of the response can be explained by the assumption that antagonistic center-surround retinal receptive fields contribute to the response, which are larger under scotopic than under photopic levels of stimulation.
[3H]ouabain binding (1.85-500 nmol/l) was evaluated in resting guinea-pig papillary muscles at 1.2-12 mmol K/l. The time course of binding was biphasic. This finding excluded a homogeneous population of non-interacting binding sites of ouabain, even though the identical susceptibility of both phases to K suggested the occupation of similarly operative receptors. Concomitant with ouabain binding, intracellular Na ion activity (aiNa) increased in the presence of 2.4 or 12 mmol K/l. Occupation of the receptor molecule by ouabain, therefore, conformed to Na-pump inhibition. Although K antagonized both ouabain binding and its effect on aiNa, the antagonistic effect on aiNa was more pronounced. The reduction of passive Na influx with depolarization as well as the stimulation of the Na pump by K presumably contributed to the antagonistic effect of K. The decrease in aiNa from 8 to 5 mmol/l, when in the absence of ouabain K was raised from 2.4 to 12.0 mmol/l, confirmed the relevance of Na fluxes. Simultaneous changes in aiNa and in the force of rested-state contractions were apparent upon addition of ouabain. At 2.4 mmol K/l, increase in aiNa raised the force of contraction by constant proportions. At 12 mmol K/l, the inotropic effect produced at comparable values of aiNa was approximately tenfold higher and was susceptible to a change in extracellular Ca concentration. Increase in aiNa, however, was differently effective on force of contraction of low as compared with high values of aiNa. The influence of resting membrane potential on electrogenic Na-Ca exchange is supposed to interfere with the inotropic effectiveness of aiNa after the cell membrane depolarized from -102 mV to -65 mV with the increase of K from 2.4 to 12 mmol/l. In view of the role of both membrane potential and aiNa not just a single mechanism appeared to be involved in the control of force of contraction.
Electrical responses to single flashes were recorded from the epipharynx and from various intranasal locations by withdrawing a nasopharyngeal electrode through the nose. The anatomical relation between the electrode and the eye ball was checked by taking an X-ray of the subject's skull. In the epipharynx and in the anterior part of the nose the responses were ERGs (a-wave, b-wave, wavelets) which were inverted in polarity. The reversal in polarity occurred when the electrode tip was underneath the posterior pole of the eye. At this electrode position and further back to the epipharynx high-frequency oscillations of increased amplitude and different waveform were recorded. It is concluded that components that change their polarity are generated by retinal dipoles oriented parallel with the electrode path while the increased oscillations recorded in the back of the nose are generated in the optic nerve by dipoles of vertical orientation.
The aim of the present study was to determine the mechanism of the positive inotropic effect of carbachol on ventricular myocardium. Carbachol produced a concentration-dependent (0.1 to 300 mumol/l) increase in contraction force on the catecholamine-depleted papillary muscle of the guinea pig without affecting the normal action potential or the slow action potential evoked in 24 mmol/l K+. Since atropine prevented the inotropic effect of carbachol, muscarinic receptors were involved. Carbachol (300 mumol/l) produced an increase in intracellular Na+-ion-activity, aiNa, by about 3 mmol/l in the quiescent muscle, and the time course of the aiNa change corresponded with the development of the positive inotropic effect as determined in the stimulated preparation (0.2 Hz). The effect of carbachol on force of contraction and on aiNa was diminished by reducing [Ca2+]0. The positive inotropic effect of carbachol was dependent on repetitive activity and was markedly enhanced in the presence of dihydro-ouabain. The results are consistent with the hypothesis, that carbachol increases the Na+ permeability of the sarcolemma via muscarinic receptors, and enhances force of contraction by stimulating the Na+-Ca2+-exchange.
Electrical mass responses of the visual system to stripe patterns of varying fineness (spatial frequency) can show either an amplitude maximum at a medium spatial frequency, a behavior termed "spatial selectivity," or a monotonic decrease in amplitude with increasing spatial frequency. The former behavior is probably mediated by neurons having a center-surround receptive field structure and the latter by neurons lacking this antagonism. The pattern-evoked human electroretinogram was studied in this report using different spatial frequencies and pattern contrasts. The positive component of the response showed a spatial selectivity only at low contrast but was not spatially selective at the highest contrast. The negative component showed a spatial selectivity at all contrast levels. The data indicate that if pattern-related responses activated by antagonistic receptive fields are to be studied, low contrast values should be employed and attention should be paid to the negative component of the response.
Pattern ERGs in response to pattern-reversal stimuli varying in spatial frequency (range: 0.2-9.03 cycles/deg) and contrast (range: 0.03-0.93) were recorded from two normal male subjects. At most spatial frequencies the response amplitude increased linearly up to the highest contrast without saturation. From the amplitude-versus-contrast plots spatial contrast-transfer functions were derived for different levels of contrast. The sensitivity of the reversal response showed a spatial selectivity around 4 cycles/deg, which was more pronounced at low, rather than at high, contrast values. Good agreement with the psychophysical contrast-sensitivity curve was found. The procedure described permits a quantitative analysis of the sensitivity of the retina to spatial contrast stimuli and could be helpful in the diagnosis of diseases of the eye and the optic nerve.
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