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Biomedical subjects

R F Miller

Publications and source records attributed to R F Miller.

At least 307 records · Page 17Linked to original sources
PubMed1985

Extracellular K+ activity changes related to electroretinogram components. I. Amphibian (I-type) retinas.

Electroretinographic (ERG) and extracellular potassium activity measurements were carried out in superfused eyecup preparations of several amphibians. Light-evoked changes in extracellular K+ activity were characterized on the bases of depth profile analysis and latency measurements and through the application of pharmacological agents that have selective actions on the retinal network. Three different extracellular potassium modulations evoked at light onset were identified and characterized according to their phenomenological and pharmacological properties. These modulations include two separable sources of light-evoked increases in extracellular K+: (a) a proximal source that is largely post-bipolar in origin, and (b) a distal source that is primarily or exclusively of depolarizing bipolar cell origin. The pharmacological properties of the distal extracellular potassium increase closely parallel those of the b-wave. A distal light-evoked decrease in extracellular potassium appears to be associated with the slow PIII potential, based on a combination of simultaneous intracellular Müller cell recordings and extracellular ERG and potassium activity measurements before and during pharmacological isolation of the photoreceptor responses. The extracellular potassium activity increases are discussed with respect to the Müller cell theory of b-wave generation.

Ambystoma↗
PubMed1985

Extracellular K+ activity changes related to electroretinogram components. II. Rabbit (E-type) retinas.

Electroretinogram (ERG) and extracellular potassium activity (K+o) measurements were carried out in isolated superfused rabbit eyecup preparations under control conditions and during the application of pharmacological agents that selectively modify the light-responsive retinal network. Light-evoked K+o changes in the rabbit (E-type) retina resemble those previously described in amphibian (I-type) retinas. Different components of the light-evoked K+o changes can be distinguished on the bases of retinal depth, V vs. log I properties, and their responses to pharmacological agents. We find two separable sources of light-evoked increases in extracellular K+: a proximal source and a distal source. The properties of the distal light-evoked K+o increase are consistent with the hypothesis that it initiates a K+-mediated current through Müller cells that is detected as the primary voltage of the electroretinographic b-wave. These experiments also support previous studies indicating that both the corneal-positive component of c-wave and the corneal-negative slow PIII potential result from K+-mediated influences on, respectively, the retinal pigment epithelium and Müller cells.

Acetylcholine↗
PubMed1985

Characterization of an extended glutamate receptor of the on bipolar neuron in the vertebrate retina.

The synaptic receptors of ON bipolar neurons are selectively activated by 2-amino-4-phosphonobutyrate, a glutamate analogue. This agent uniquely distinguishes these receptors from other types of excitatory amino acid receptors found in the retina. Various glutamate and aspartate analogues were used to assess the structure-activity characteristics of this receptor. The results suggest that it represents one class of glutamate receptor which can be distinguished by its preferential activation by acidic amino acid analogues that match the extended conformation of glutamate.

Aminobutyrates↗
PubMed1983

An excitatory amino acid antagonist blocks cone input to sign-conserving second-order retinal neurons.

cis-2,3-Piperidinedicarboxylic acid (PDA), an excitatory amino acid antagonist, reversibly blocked cone input to OFF bipolars and horizontal cells, whereas ON bipolars were relatively unaffected. Kainic acid effects were also blocked, indicating a postsynaptic mechanism of action. The use of PDA helps to characterize one of two classes of excitatory amino acid synaptic receptors that mediate cone influence in the outer retina.

Amino Acids↗
PubMed1983

Intracellular chloride in retinal neurons: measurement and meaning.

Intracellular chloride activity measurements were obtained from mudpuppy retinal neurons using dual microelectrodes, one of which was made chloride-selective by filling the tip with chloride liquid ion exchange resin. In addition ionic substitution experiments were carried out in the perfused retina-eyecup preparation of the mudpuppy. A comparison of the membrane potential and calculated chloride equilibrium potential shows that retinal neurons differ in relative transmembrane chloride distribution. Ganglion cells have an ECl more negative than the resting membrane potential, whereas amacrine cells have a passive distribution of chloride. Horizontal cells have chloride distributed such that an increase in chloride conductance is depolarizing. On-bipolars have a chloride distribution similar to that of horizontal cells whereas off-bipolars show either passive distribution or some chloride accumulation. These findings are consistent with the idea that chloride ions may play a role as a depolarizing driving force for electrogenic activity of horizontal cells and on-bipolars. Results with Cl substitution experiments are consistent with this interpretation.

Animals↗
PubMed1983

Electroanatomy of a unique amacrine cell in the rabbit retina.

Intracellular electrophysiological recordings were obtained from a specialized class of "starburst" amacrine cells by using an isolated superperfused retina-eyecup preparation of the rabbit. These cells were injected intracellularly with horseradish peroxidase and identified with light microscopy. A computer-controlled image-processing system was used to map and display the three-dimensional dendritic organization and provide information on length and sublaminar distribution of dendritic processes. Starburst amacrines show an unusual dendritic architecture that includes thin intermediate dendritic segments. Analysis with steady-state cable equations suggests that these thin segments may provide electrical isolation of distal processes, raising the possibility that a single dendrite, which lies beyond the thin segment, may constitute a functional subunit of the cell.

Action Potentials↗
PubMed1983

The role of excitatory amino acid transmitters in the mudpuppy retina: an analysis with kainic acid and N-methyl aspartate.

A variety of glutamate and aspartate analogues were used to characterize the excitatory amino acid receptors in the mudpuppy retina. This approach revealed two general classes of receptors which were represented by the agonists kainic acid and N-methyl aspartic acid. Kainic acid was found to be a potent photoreceptor transmitter agonist on all three types of second-order neurons, and it was a powerful excitant of amacrine and ganglion cells. N-Methyl aspartate had little effect in the outer retina, but it had potent stimulatory effects on inner retinal neurons. N-Methyl aspartate antagonists selectively blocked light responses in some sustained OFF ganglion cells. These results suggest that both photoreceptors and bipolar neurons may use glutamate Or an analogue, whereas aspartate may be utilized by a class of sustained ON amacrine cells.

Animals↗
PubMed1982

A physiological and morphological study of the horizontal cell types of the rabbit retina.

A perfused, isolated retina-eyecup preparation of the rabbit was utilized to correlate the physiology and morphology of horizontal cells. Neurons were physiologically characterized by intracellular recording techniques and subsequently stained with intracellular iontophoretically injected horseradish peroxidase for morphological identification. Three types of rabbit horizontal cell recordings have been differentiated, based on variations in response waveform, amplitude-intensity properties, and area summation characteristics. These three types have been unequivocally associated with the axonless A-type horizontal cells and the somatic and axon terminal endings (each displaying its own distinct physiology) of B-type horizontal cells first described in studies using Golgi-impregnation techniques (Fisher and Boycott, '74). In addition, the sizes of A-type horizontal cells were found to be directly related to their retinal eccentricities from the optic desk. However a unique subclass of A-type cells has been discovered (elongated or Ae type) which displayed the largest dendritic field of any cells studied here, yet had the smallest eccentricities--within 1.4 mm of the optic disk. Moreover, elongated A-type cells exhibited long asymmetrical dendritic fields which were oriented parallel with the visual streak. The unique asymmetry and orientation of these cells suggests that they may have orientation-biased receptive field properties. Physiological evidence for an orientation-biased horizontal cell is presented in support of this notion.

Animals↗
PubMed1981

Peptides influence retinal ganglion cells.

Neurotensin, substance P and (D-Ala2, Met5)-enkephalinamide were iontophoresed onto ganglion cells of the amphibian retina. Substance P and neurotensin were found to be excitatory while (D-Ala2, Met5)-enkephalinamide suppressed all types of ganglion cells. These findings are consistent with a functional role for peptides in the vertebrate retina.

Amphibians↗
PubMed1981

An intracellular electrophysiological study of the ontogeny of functional synapses in the rabbit retina. I. Receptors, horizontal, and bipolar cells.

An isolated perfused retina-eyecup of the rabbit neonate was used to study the functional maturation of synaptic interactions in the outer plexiform layer. Intracellular recordings from receptors, horizontal cells, hyperpolarizing and depolarizing bipolar cells were obtained in the adult and at different stages of maturation. Three types of horizontal cells could be distinguished based on the relative amount of rod and cone input, response wave form, receptive field diameter, and amplitude-intensity relationships. Two of the horizontal cell types were encountered with sufficient frequency such that maturation of these response characteristics could be followed over the developmental period of this study (8 days-adult). The growth rate of the amplitude-intensity relationships was different for the two commonly encountered types of horizontal cells; the small diameter receptive field type achieved an adultlike amplitude-intensity range at an earlier age than the large field type. Immature bipolar cell responses were initially monophasic potentials with transient-sustained components appearing at a later stage. Center surround antagonism of bipolar cells developed after center-mediated responses were first observed. This suggests some secondary modifications during synaptogenesis are responsible for the late maturation of center surround antagonism. The morphological appearance of synaptic contacts during different stages of synaptogenesis is discussed in reference to the different phases of functional, synaptic interactions of this study. It appears that some synapses in the vertebrate retina are functional at a time when synaptic structure is incomplete, based on ultrastructural observation. Maturation of receptive field diameter and amplitude-intensity function is discussed in relationship to possible presynaptic and postsynaptic mechanisms which may influence this growth.

Age Factors↗
PubMed1981

An intracellular electrophysiological study of the ontogeny of functional synapses in the rabbit retina. II. Amacrine cells.

Intracellular recordings in an isolated perfused retina-eyecup preparation of the neonate rabbit were used to study the physiological development of amacrine cells. By responding with transient depolarizations at the onset and termination of illumination, mature mammalian on-off amacrine cell recordings appeared similar to those described in lower vertebrates. However, immature amacrine cell recordings showed a predominantly on response, with off responses small and easily fatigued during repetitive stimulation. This underdeveloped off component of the amacrine cell response could also be abolished by decreasing the area of receptive field that was stimulated. The more slowly developing off component may reflect a different maturation rate of depolarizing (on) and hyperpolarizing (off) bipolar cells. In addition, properties of the maturing inner plexiform layer were examined with extracellular recordings of the proximal negative response (PNR). The PNR showed evidence of easy fatigability more evident in the off response. These observations are consistent with the idea that the initial phase of light sensitivity is associated with labile synaptic input from bipolar cells.

Animals↗
PubMed1981

2-amino-4-phosphonobutyric acid: a new pharmacological tool for retina research.

Information processing in the vertebrate retina occurs in two separate channels known as ON and OFF channels. When intracellular electrophysiological recordings were obtained from the perfused retina-eyecup preparation of the mud-puppy (Necturus maculosus), the addition of 2-amino-4-phosphonobutyric acid to the bathing medium blocked all responses in the ON channel but left intact the OFF responses including OFF ganglion cell discharge. 2-Amino-4-phosphonobutyric acid blocks the light response of the ON bipolar cell by mimicking the endogenous photoreceptor transmitter.

Action Potentials↗
PubMed1981

Long-term hemodynamic and metabolic effects of trimazosin in essential hypertension.

The long-term effects of trimazosin (TMZ) were studied in 26 male patients with mild essential hypertension. After a 2 wk single-blind placebo (P) period, 13 patients were randomly selected to receive TMZ and 13 P; they were followed for an additional 8 wk. TMZ was given in incremental doses of 25 to 50, 100 to 200, and finally 300 mg three times a day. The patients were seen at the clinic every 2 wk and their arterial pressures (AP) and heart rates (HRs) were measured in the supine (5 min) and upright (2 min) position. Blood chemistries, blood count, plasma volume (PV), plasma renin activity (PRA), plasma aldosterone (PA), and cardiac output (CO) were determined by ultrasound at the end of P and TMZ periods. TMZ decreased the AP and total peripheral resistance (TPR) at the higher dosages, but had no effect on PV, PRA, PA, CO, HR, or blood chemistry determinations. No effects were observed on any of the above parameters after P. We conclude that (1) TMZ is an effective and safe antihypertensive, (2) it lowers AP through reduction of TPR, and (3) its effect is dose related.

Antihypertensive Agents↗