Dopamine influences the light peak in the perfused mammalian eye.

Dopamine, cis-flupenthixol, and dibutyryl cAMP affected the standing potential and light-evoked responses of the perfused cat eye in vitro. At micromolar concentrations, dopamine, a retinal neurotransmitter, increased the standing potential of the eye. At slightly higher concentrations, dopamine abolished the "light peak," a slow voltage response to light generated by the retinal pigment epithelium. The light peak was depressed by cis-flupenthixol, a dopamine antagonist, at micromolar concentrations. Dibutyryl cAMP produced effects similar to those produced by dopamine. A possible interpretation is that the generation of the light peak involves a catecholamine-stimulated adenylate cyclase in retinal pigment epithelium that is influenced by dopamine released from retinal neurons.

Theophylline abolishes the light peak in perfused cat eyes.

Theophylline, a phosphodiesterase inhibitor, was applied to the arterially perfused cat eye in vitro. At a concentration of 850 microM, theophylline abolished the light peak of the DC-ERG and led to a 20% increase in perfusate flow to the eye. The effects were reversible. An experimentally-induced increase in flow per se by 20% resulted in a slight enhancement of the light peak. The data suggest the involvement of cyclic nucleotides in the generation of the light peak. Theophylline also caused a decrease in the standing potential of the eye, an increase in the b-wave amplitude, and a decrease in the c-wave amplitude in a dose-dependent and reversible manner.

A reweighting of receptor mechanisms in the ground squirrel retina: PIII and B-wave spectral sensitivity functions.

PIII and b-wave spectral sensitivity functions were measured under various adapted conditions in the 13-lined ground squirrel. The PIII was isolated by intravitreal injection of sodium L-aspartate. Under the conditions studied, the PIII spectral sensitivity function always fitted the absorption spectrum of a 518 +/- 3 mm Dartnall nomogram. This suggests that of the three photoreceptors ('rod-like', 'blue' cone and 'green' cone) present in the 13-lined ground squirrel the green cones are the overwhelming majority. The dark-adapted b-wave had two components; a b1-wave with a spectral sensitivity that fitted a 516 +/- 1 nm Dartnall nomogram and a b2-wave with a spectral sensitivity that fitted a 502 +/- 4 nm Dartnall nomogram. The light-adapted b-wave had a spectral sensitivity that fitted a 516 +/- 2 nm Dartnall nomogram.

Light adaptation in cone photoreceptors: the occurrence and significance of unitary adaptive strength.

The behavior of "peak response-log intensity" functions generated by the "dark glasses model" is examined and is shown to describe previously observed light adapted behavior in cone photoreceptors. The models of Boynton and Whitten (1970) and Norman and Werblin (1974) are closely related to the dark glasses model--the Boynton-Whitten model being more specific and the Normann-Werblin model more general. For the models, a certain parameter relationship will produce systems which have optimal intensity discriminative capacities. When the data are fitted, this parameter relationship--unitary adaptive strength--seems to emerge. Possible evolutionary and psychophysical implications are discussed.

Signal transmission through a metabolic cycle follows the compression hypothesis or a weak Weber's law.

Biological signal transduction often involves a metabolic cycle in which the flux at one point is driven by the input signal and the concentration of one of the metabolites of the cycle serves as the output signal. A kinetic analysis of such a metabolic cycle is made under an assumption that the law of mass action applies. The resultant kinetic model can produce a response that overshoots, quickens, and eventually saturates as the input intensity is increased. The possible model behavior ranges parametrically from non-adaptive (compression hypothesis) to weakly adaptive (limited Weber's law).

A molecular basis for Weber's law.

A mathematical model is presented that obeys a strong form of Weber's law--over a range of adapting and stimulus intensities, equal contrast stimuli evoke identical responses. To account for the strong Weber's law, the adaptive stage in the proposed model employs a "delayed" reverse reaction along with a power-law input. It is suggested that this Weber's law mechanism is responsible for a slow, voltage-uncorrelated component of adaptation in the vertebrate photoreceptor. A plausible biochemical mechanism is the G-protein cycle with phosphorylation of photoactivated photopigment (and binding of arrestin to the phosphorylated photopigment) as the adaptive process. In an Appendix, features of the general model and implications of a specific biochemical model are examined by computer simulation.

Linking quantal absorption rate to the visual response.

A photochemical system is proposed that offers a possible link between the rate of quantal absorption and the visual response. In the proposed system the time courses of the concentrations of certain photoproducts turn out to be equal to the quantal absorption rate passed through various linear filters. The proposed system is consistent with the cone pigment kinetics proposed by Rushton (1958). The system produces afterimages and can provide Weber's law behavior.

A model for light adaptation: producing Weber's law with bleaching-type kinetics.

An "adaptation model" having two stages is introduced and its mathematical properties are examined. The two stages are the "adaptive process" (parameter Kb), which has bleaching-type kinetics, and the "response function" (parameters Kr and n), which incorporates response saturation. In order to study the increment threshold functions generated by the "adaptation model" the concept of a "detector" is required. It is demonstrated that without an adaptive process the compression hypothesis, in the form of the "difference equation", produces increment threshold functions which saturate and do not obey Weber's law. It is then shown that an adaptive process with bleaching-type kinetics can prevent saturation and produce Weber's law behavior provided that the "adaptive strength" of the system exceeds the "detector sensitivity".

Light-evoked changes in near-infrared transmission by the ON and OFF channels of the anuran retina.

We have developed an optical method to monitor the activity of the ON and OFF channels in the anuran retina. The change in the fraction of near infrared that is transmitted transversely through the retina in an eyecup slice is monitored during stimulation by visible, green light. Near-infrared transmission increases both at the onset and at the termination of a step stimulus. This "ON/OFF" response is maximal in the neural retina. Sodium L-aspartate, which blocks the light-evoked activity of post-photoreceptor neurons, abolishes the "ON/OFF" response. L-AP4, used as a selective blocker of the ON channel, reduces the "ON" component and has little or no effect on the "OFF" component. The "ON" and "OFF" processes observed optically are distinct from those that generate the b- and d-waves of the electroretinogram, and the "ON" and "OFF" components may be superior to the b- and d-waves as indicators of ON and OFF channel activity. The optical method is almost as simple as electroretinography and has the advantages that responses can be spatially localized with ease.

Adaptation in cones. A general model.

Three features appear to characterize steady-state light adaptation in vertebrate cone photoreceptors: (a) the shape of the "log intensity-response" curve at different levels of adaptation is the same, the only change with adaptation is in the position of the point on the curve about which the cones operate; (b) at high adapting intensities the operating point becomes fixed in position; (c) this fixed position is at the steepest point of the log intensity-response curve. These three features can be described by a mathematical model.

Regulation of cyclic GMP metabolism in toad photoreceptors. Definition of the metabolic events subserving photoexcited and attenuated states.

Photoreceptor metabolism of cGMP and its regulation were characterized in isolated toad retinas by determining the intensity and time dependence of light-induced changes in the following metabolic parameters: cGMP hydrolytic flux determined by the rate of 18O incorporation from 18O-water into retinal guanine nucleotide alpha-phosphoryls; changes in the total (protein-bound and unbound) concentrations of the guanine nucleotide metabolic intermediates; and changes in the concentration of metabolic (unbound) GDP calculated from the fraction of the alpha-GDP that undergoes labeling with 18O. The latter is interpreted to reflect the state of the equilibrium between GDP- and GTP-complexed forms of G-protein. With narrow band 500 nm light that preferentially stimulates red rod photoreceptors, a range of intensities covering approximately 5 log units produced increases of over 10-fold in cGMP metabolic flux. However, the characteristics of the cGMP metabolic response over the first 2.5 log units of intensity are readily distinguishable from those at higher intensities which exhibit progressive attenuation by an intensity- and time-dependent process. Over the range of low intensities (0.6-3 log photons.micron-2.s-1) the metabolic response is characterized by 1) increases in cGMP hydrolytic flux of up to 8-fold as a logarithmic function of intensity of photic stimulation that are sustained for at least 200 s; 2) small increases or no change in the concentration of total cGMP; 3) large increases of up to 10-fold in the concentration of metabolically active GDP as a linear function of intensity with no significant change in the tissue concentrations of total GDP or GTP; and 4) amplification of the photosignal by the metabolism of approximately 10,000 molecules of cGMP per photoisomerization with the major site of amplification at the level of the interaction of bleached rhodopsin with G-protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine triphosphate utilization rates and metabolic pool sizes in intact cells measured by transfer of 18O from water.

The hydrolytic rates and metabolic pool sizes of ATP were determined in intact cells by monitoring the time courses of 18O incorporation from 18O-water into the gamma-phosphoryl of ATP and orthophosphate. To calculate the rate of ATP hydrolysis, a kinetic model is used to fit the time course of the 18O labeling. The size of the metabolic pool of ATP is calculated from the 18O distribution after isotopic equilibrium has been achieved. Metabolic pools have a binomial distribution of 18O whereas nonmetabolic pools exhibit negligible 18O labeling. The application and limitations of this approach are illustrated with data from isolated toad retinas and human platelets. At 22 degrees C, the time constant of ATP hydrolysis in the dark-adapted toad retina is about 30 s. Under these conditions, over 80% of the retinal ATP is involved in high-energy phosphate metabolism. It is calculated that when cGMP metabolic flux in the photoreceptors is maximally stimulated by light, it accounts for 10% of the ATP utilization by the entire retina. The time constant of ATP hydrolysis in human platelets at 37 degrees C is approximately 1 s, and 60% of the platelet ATP is involved in energy metabolism.

Evidence for compartmentalized adenylate kinase catalysis serving a high energy phosphoryl transfer function in rat skeletal muscle.

The first characterization of the kinetics and subcellular compartmentation of adenylate kinase activity in intact muscle has been accomplished using rat diaphragm equilibrated with [18O]water. Rates of adenylate kinase-catalyzed phosphoryl transfer were measured by appearance of 18O-labeled beta-phosphoryls in ADP and ATP resulting from the transfer to AMP of newly synthesized 18O-labeled gamma-ATP. Unique features of adenylate kinase catalysis were uncovered in the intact cell not predictable from cell free analysis. This enzyme activity, which in non-contracting muscle is limited to 1/1000 of the estimated Vmax (cell free) apparently because of restricted ADP availability, is localized in subcellular compartments that increase in size and/or number with contractile frequency. Contraction also causes frequency-dependent increments in adenylate kinase velocity (22-fold at 4 Hz) as does oxygen deprivation (35-fold). These enhanced rates of adenylate kinase activity, equivalent to processing all the cellular ATP and ADP in approximately 1 min, occur when levels of ATP, ADP, and AMP are maintained very near their basal steady state. These characteristics of the dynamics of adenylate kinase catalysis in the intact cell demonstrate that rapid rates of AMP production from ADP are balanced by equally rapid rates of AMP phosphorylation with no net synthesis or accumulation of any adenine nucleotide. This rapid processing of nucleotide phosphoryls conforms to a proposed scheme whereby the adenylate kinase system provides the unique function of transferring, as beta-ADP, high energy phosphoryls generated by glycolytic metabolism to ATP-utilizing components in muscle.