Site of action potential initiation in amphibian retinal ganglion cells.

1. We applied morphological, pharmacological, electrophysiological, and computer simulation techniques to analyze the origin of impulse initiation in amphibian retinal ganglion cells. 2. Morphological studies of retinal ganglion cells in the mudpuppy (Necturus maculosus) and larval tiger salamander (Ambystoma tigrinum) were carried out with the use of either retrograde or intracellular labeling with horseradish peroxidase. These studies identified a characteristic thinning of the axon that begins after the initial segment of axon emerges from the ganglion cell soma or primary dendrite. Morphometric analysis of the thin segment revealed an average length of 74 microns with a standard deviation of 22 microns. For 20 conventionally placed ganglion cells, the length of the thin segment could not be correlated with soma size, initial segment diameter, or distance from the optic disk. There was also little or no correlation for seven displaced ganglion cells. The diameter of the thin segment was below reliable estimation by light microscopy. 3. We studied the possible significance of the thin axonal segment for ganglion cell impulse generation through a combination of electrophysiological recordings (intracellular and whole-cell recordings) together with computer modeling experiments. 4. Electrophysiological experiments are consistent with the idea that the thin segment and cell soma are less excitable than the initial segment region, which appears to be the principal site of initiation of the nerve impulse. The initial segment is that portion of the axon that is bounded by the soma (or proximal dendrite) at its origin and the thin segment at its distal end. 5. Computer simulations of impulse activation were carried out with the use of two different anatomic constraints: one class of simulations did not take into account the thin segment and assumed uniform cylinder conditions, whereas the other class of simulations included a model of the thin axonal segment. These comparative simulations indicate that the thin segment must contain a relatively high density of voltage-gated Na+ channels and support impulse traffic to account for physiological observations on orthodromic and antidromic impulse propagation. In addition, to match the physiological recordings, it is necessary for both the initial segment and the soma compartments to contain moderately high levels of Na+ channels. 6. Our physiological and simulation studies are consistent with the idea that the nerve impulse is normally initiated in the initial segment of axon and then spreads to activate a somatic impulse in the retrograde direction and the axonal impulse in the anterograde direction.(ABSTRACT TRUNCATED AT 400 WORDS)

A prospective evaluation of myocardial contusion: correlation of significant arrhythmias and cardiac output with CPK-MB measurements.

Over a nine-month period, patients with chest trauma were prospectively evaluated for myocardial contusion. Ninety-two patients with evidence of anterior chest trauma were entered into the study and had 1) an ECG on admission and daily for three days; 2) monitoring of the myocardial band fraction of creatine phosphokinase (CPK-MB) on admission and every eight hours for 24 hours; 3) continuous electrocardiographic Holter monitoring for three to five days; and 4) noninvasive pulsed-Doppler cardiac output measurements daily for three days. Twenty-three patients developed 25 significant arrhythmias (SARRs): 1 atrial fibrillation, 1 AV dissociation, 5 supraventricular tachycardias, and 18 paroxysmal ventricular tachycardias. Cardiac outputs were significantly higher in those patients without SARRs. The CPK-MB levels correlated with the SARRs but were neither sensitive nor specific. No patients required specific therapy and none developed adverse sequelae of the SARRs. We conclude that 1) CPK-MB monitoring should not be routinely used for screening and diagnosis; 2) continuous arrhythmia monitoring deserves further clinical investigation but not routine application; 3) stable patients at risk for myocardial contusion should be monitored for 24 hours; and 4) the Abbreviated Injury Score for "minor" myocardial contusion should be deleted for purposes of ISS tabulation.

Modeling the repetitive firing of retinal ganglion cells.

A kinetic model for the repetitive firing of retinal ganglion cells was synthesized from voltage-clamp data and evaluated by comparison with whole cell recordings from ganglion cells in the intact tiger salamander retina. Five distinct channels were included in the model and were sufficient to describe the physiologically observed frequency/current relationship in response to various levels of cell depolarization.

Kainate receptor-mediated synaptic currents in mudpuppy inner retinal neurons reduced by D-O-phosphoserine.

1. The effects of D-O-phosphoserine (DOS) were examined on proximal neurons in the superfused mudpuppy retinal-eyecup preparation by measuring their synaptically evoked whole-cell currents with the use of patch-clamp electrodes. 2. DOS reduced the light-evoked excitatory postsynaptic potentials (EPSPs) of amacrine and ganglion cells. This suppression was present even though the center responses of both ON- and OFF-bipolar cells were unaffected by DOS. 3. When recordings were done under voltage-clamp conditions. DOS diminished the magnitude of light-evoked synaptic currents associated with a reduction in synaptic conductance. 4. To determine which acidic amino acid receptor mediated the network-selective action of DOS, various glutamate agonists were tested against this excitatory amino acid receptor (EAAR) antagonist. DOS blocked the depolarizing effects of kainate (KA), but not those of N-methyl-D-aspartate (NMDA) or quisqualate (QQ). Thus DOS was a selective KA antagonist, and KA receptors appear to be the dominant EAAR subtype that mediates synaptic inputs into the inner retina of the mudpuppy.

Traumatic trochanteric bursitis.

The trochanteric bursa is anatomically quite susceptible to traumatic injury. However, specific reports of traumatic trochanteric bursitis in the literature are lacking. This may be due to failure to recognize this condition and to differentiate it from other pain syndromes involving the hip. This case report demonstrates the clinical presentation and management of traumatic trochanteric bursitis.

Measurement of passive membrane parameters with whole-cell recording from neurons in the intact amphibian retina.

1. Whole-cell recordings have been obtained from intact, photoactive retinal neurons using patch-clamp electrodes in the amphibian superfused retina eyecup preparation. 2. After removal of the vitreous humor from the surface of the retina, using a collagenase with low tryptic activity, high-resistance seals (1-10 G omega) could be formed between the patch pipette and the cell membrane by applying mild suction to the pipette. Additional suction broke the membrane patch and provided continuity between the low-resistance pipette and the interior of the neuron. 3. Measurements of input resistance and time constant were obtained from bipolar, amacrine, and ganglion cells. Assuming the membrane capacitance was 1 microF/cm2, time constant data were used to derive the specific membrane resistance. The average specific membrane resistance for the inner retinal neurons in our sample was 68,000 omega.cm2. 4. Analysis of the charging curve induced by a brief current pulse applied to the soma was used to analyze the average electrotonic length of dendrites. The charging curves of some ganglion cells were well represented by a single exponential, suggesting that they were essentially isopotential. 5. The voltage decay along an equivalent cylinder model of a ganglion cell was calculated, using the experimentally obtained values of membrane resistance to compute decay of steady-state voltages along the dendritic tree. The calculations indicate that with the high membrane resistance values implied by this study, the electrotonic length of dendritic cables were short, and there may be relatively little attenuation of the synaptic potentials irrespective of their location along the dendritic tree.

Do N-methyl-D-aspartate receptors mediate synaptic responses in the mudpuppy retina?

Whole-cell recordings of amacrine and ganglion cells in the superfused retina-eyecup preparation of the mudpuppy were obtained in order to determine which excitatory amino acid receptor (EAAR) subtype mediates the synaptic responses of these neurons. All third-order retinal neurons tested were depolarized by kainic acid (KA, N-methyl-D-aspartate (NMDA), and quisqualate (QQ). The responses evoked by NMDA were blocked by the addition of D-2-amino-5-phosphonovaleric acid (D-AP5) and D-2-amino-7 phosphonoheptonoic acid (D-AP7) to the perfusate. When the actions of exogenously applied NMDA were completely blocked by D-AP5 and D-AP7, the light-evoked responses of inner retinal neurons persisted without any apparent reduction or, alternatively, a slight enhancement of the response was observed. Light-evoked responses of bipolar, amacrine, and ganglion cells associated with the On pathway were attenuated by L-AP5 in a manner similar to its lower-order homolog L-2-amino-4-phosphonobutyrate (AP4); nevertheless, L-AP5 was not an effective NMDA antagonist. Although synaptic transmission between retinal second- and third-order neurons appears to be mediated by EAARs, the NMDA receptor does not appear to play a prominent role under our experimental conditions. Nevertheless, our results suggest that the racemic mixture of AP5 should not be used as an NMDA antagonist in retinal research, due to the AP4-like actions of its L-enantiomer.

Barium reverses the transretinal potassium gradient of the amphibian retina.

Barium chloride (Ba2+) was added to the bathing medium of the perfused retina-eyecup preparation of the tiger salamander. The electroretinogram (ERG) and intraretinal extracellular potassium activity ([K+]o) were analyzed using a double-barrel electrode, one of which was ion-selective for K+. The action of Ba2+ on the ERG was to attenuate the c-wave/slow PIII complex. In addition, Ba2+ dramatically decreased the [K+]o in the outer retina, enough to reverse the transretinal potassium gradient. These findings, together with the known properties of Müller cell K+ channels, form the basis of an explanation of why Ba2+ blocks slow PIII and not the b-wave of the ERG.

Kynurenic acid distinguishes kainate and quisqualate receptors in the vertebrate retina.

Excitatory amino acid receptors (EAARs) underlie major synaptic pathways in the brain, retina and spinal cord. Several subclasses of EAARs have been proposed, based on pharmacological studies using a variety of agonists and antagonists. Kynurenic acid (Kyn), a metabolite of tryptophan, has been recently proposed as a potent EAAR antagonist. In this report, we show that Kyn can be used to separate two distinct classes of EAAR in the vertebrate retina: it blocks kainic acid (KA) responses but has minimal effects on responses mediated by quisqualate (QQ). At concentrations which block the KA responses, Kyn also blocks the light-evoked synaptic responses of all types of third-order neurons in the retina. These results suggest that KA receptors are the major receptor subtypes which underlie synaptic transmission and that QQ receptors are minimally utilized by light-activated pathways under the conditions of our experiments.