Synchronous Ca(2+) oscillation emerges from voltage fluctuations of Ca(2+) stores

Synchronous Ca(2+) oscillation occurs in various cell types to regulate cellular functions. However, the mechanism for synchronization of Ca(2+) increases between cells remains unclear. Recently, synchronous oscillatory changes in the membrane potential of internal Ca(2+) stores were recorded using an organelle-specific voltage-sensitive dye [Yamashita et al. (2006) FEBS J273, 3585-3597], and an electrical coupling model of the synchronization of store potentials and Ca(2+) releases has been proposed [Yamashita (2006) FEBS Lett580, 4979-4983]. This model is based on capacitative coupling, by which transient voltage changes can be synchronized, but oscillatory slow potentials cannot be communicated. Another candidate mechanism is synchronization of action potentials and ensuing Ca(2+) influx through voltage-dependent Ca channels. The present study addresses the question of whether Ca(2+) increases are synchronized by action potentials, and how oscillatory store potentials are synchronized across the cells. Electrophysiological and Ca(2+)-sensitive fluorescence measurements in early embryonic chick retina showed that synchronous Ca(2+) oscillation was caused by releases of Ca(2+) from Ca(2+) stores without any evidence of action potentials in retinal neuroepithelial cells or newborn neurons. High-speed fluorescence measurement of store membrane potential surprisingly revealed that the synchronous oscillatory changes in the store potential were periodic repeats of a burst of high-frequency voltage fluctuations. The burst coincided with a Ca(2+) increase. The present study suggests that synchronization of Ca(2+) release is mediated by the high-frequency fluctuation in the store potential. Close apposition of the store membrane and plasma membrane in an epithelial structure would allow capacitative coupling across the cells.     

Oscillatory potentials of the cat retina: effects of adrenergic drugs

When reserpine was used as a monoaminergic depletion agent, a diminution or suppression of certain components of the oscillatory potentials of the electroretinogram of the cat was observed. Administration of L-Dopa to previously reserpinized cats restored the altered OP components. The possible interference of systematic disturbances provoked by the drugs was studied by means of artificial variations of blood pressure. Results reported in this paper suggest that reserpine and L-Dopa are acting on catecholamine-dependent retinal structures, probably the dopamine-containing population of amacrine cells. An hypothesis is advanced concerning the possible role of tangential structures in the generation of the oscillatory potentials of the retina.     

Dopamine D1 Receptors Regulate the Light Dependent Development of Retinal Synaptic Responses

Retinal synaptic connections and function are developmentally regulated. Retinal synaptic activity plays critical roles in the development of retinal synaptic circuitry. Dopamine receptors have been thought to play important roles in the activity-dependent synaptic plasticity in central nervous system. The primary goal of this study is to determine whether dopamine D1 receptor regulates the activity-dependent development of retinal light responsiveness. Accordingly, we recorded electroretinogram from wild type mice and mice with genetic deletion of D1 dopamine receptor (D1−/− mice) raised under cyclic light conditions and constant darkness. Our results demonstrated that D1−/− mice have reduced amplitudes of all three major components of electroretinogram in adulthood. When the relative strength of the responses is considered, the D1−/− mice have selective reduction of the amplitudes of a-wave and oscillatory potentials evoked by low-intermediate intensities of lights. During postnatal development, D1−/− mice have increased amplitude of b-wave at the time of eye-opening but reduced developmental increase of the amplitude of b-wave after eye opening. Light deprivation from birth significantly reduced the amplitudes of b-wave and oscillatory potentials, increased the outer retinal light response gain and altered the light response kinetics of both a- and b-waves of wild type mice. In D1−/− mice, the effect of dark rearing on the amplitude of oscillatory potentials was diminished and dark rearing induced effects on the response gain of outer retina and the kinetics of a-wave were reversed. These results demonstrated roles of dopamine D1 receptor in the activity-dependent functional development of mouse retina.     

Environmental Enrichment Protects the Retina from Early Diabetic Damage in Adult Rats

Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Available treatments are not completely effective. We analyzed the effect of environmental enrichment on retinal damage induced by experimental diabetes in adult Wistar rats. Diabetes was induced by an intraperitoneal injection of streptozotocin. Three days after vehicle or streptozotocin injection, animals were housed in enriched environment or remained in a standard environment. Retinal function (electroretinogram, and oscillatory potentials), retinal morphology, blood-retinal barrier integrity, synaptophysin, astrocyte and Müller cell glial fibrillary acidic protein, vascular endothelial growth factor, tumor necrosis factor-α, and brain-derived neurotrophic factor levels, as well as lipid peroxidation were assessed in retina from diabetic animals housed in standard or enriched environment. Environmental enrichment preserved scotopic electroretinogram a-wave, b-wave and oscillatory potential amplitude, avoided albumin-Evan''s blue leakage, prevented the decrease in retinal synaptophysin and astrocyte glial fibrillary acidic protein levels, the increase in Müller cell glial fibrillary acidic protein, vascular endothelial growth factor and tumor necrosis factor-α levels, as well as oxidative stress induced by diabetes. In addition, enriched environment prevented the decrease in retinal brain-derived neurotrophic factor levels induced by experimental diabetes. When environmental enrichment started 7 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that enriched environment could attenuate the early diabetic damage in the retina from adult rats.     

Magnetically recorded oscillatory responses to luminance stimulation in man

Fast-frequency (ca. 100–110 Hz) oscillatory potentials superimposed on waves N2 and P2 of conventional broad-band VEP were magnetically recorded in man from occipital locations in response to monocular transient flash stimulation with full-field flashes (3.5 cd s⁻¹ m⁻² intensity) and in spots (1, 1.5, or 2.0 cm in diameter). These oscillations proved replicable between- and within-subject and were phase-locked to retinal oscillatory potentials, with maximum correlation at approximately 35 ms and mean delay (as measured between the first measurable peaks) of 27.4±1.6 ms. When stimuli were in spots at increasing eccentricity (5, 15, or 25°) from foveal fixation, broad-band VEP were recorded regardless of diameter and eccentricity of spot, whereas oscillatory responses were not detectable at eccentricity of, or greater than, 15°. This observation suggests that broad-band VEP and the oscillatory response are generated by (partly) distinct neuronal populations and/or functional arrangements and that there is some functional connection between cortical oscillatory responses and stimulus-related events triggered in central retina.     

Retinal mechanisms of visual adaptation in the skate

Electrical potentials were recorded from different levels within the skate retina. Comparing the adaptive properties of the various responses revealed that the isolated receptor potential and the S-potential always exhibited similar changes in sensitivity, and that the b-wave and ganglion-cell thresholds acted in concert. However, the two sets of responses behaved differently under certain conditions. For example, a dimly iluminated background that had no measurable effect on the senitivities of either of the distal responses, raised significantly the thresholds of both the b-wave and the ganglion cell responses. In addition, the rate of recovery during the early, "neural" phase of dark adaptation was significantly faster for the receptor and S-potentials than for the b-wave or ganglion cell discharge. These results indicate that there is an adaptive ("network") mechanism in the retina which can influence significantly b-wave and gaglion cell activity and which behaves independently of the receptors and horizontal cells. We conclude that visual adaptation in the skate retina is regulated by a combination of receptoral and network mechanisms.     

Rod and Cone Function in Patients with KCNV2 Retinopathy

Background

To investigate rod and cone function and disease mechanisms in patients with KCNV2 retinopathy.

Methodology/Principal Findings

Psychophysical examinations as well as detailed electrophysiological examinations with Ganzfeld and multifocal electroretinogram (ERG) were performed to study response dynamics. Additionally, fundus photography, autofluorescence imaging and spectral domain OCTs were carried out for morphological characterization. Molecular genetic analysis revealed compound heterozygosity in five patients and homozygosity for the KCNV2 gene in one patient. The mutations resulted in complete absence of Kv8.2 subunits in three patients (no protein group, NOP), while the other three patients expressed mutant Kv8.2 subunits resulting in altered Kv2.1/Kv8.2 heteromeric or residual Kv2.1 homomeric potassium channel function (altered protein group, ALP). Although more advanced morphological changes were visible in the NOP group, a clear functional difference between the two groups could not be observed. All patients showed characteristic dynamics of the b-wave intensity-response function, however, scotopic b-wave response amplitudes were within normal limits. We also observed severely reduced oscillatory potentials.

Conclusions/Significance

A specific genotype-phenotype correlation in retinal function could not be demonstrated. KCNV2 mutations cause a unique form of retinal disorder illustrating the importance of K⁺-channels for the resting potential, activation and deactivation of photoreceptors, while phototransduction remains unchanged. The reduced oscillatory potentials further suggest an altered function of the inner retina. Besides the characteristically steep amplitude-versus-intensity relationship, flicker responses at intermediate frequencies (5–15 Hz) are significantly reduced and shifted in phase.     

Entrainment of oscillatory neural activity in the cat's lateral geniculate nucleus

Oscillatory neural activity in the frequency range 7–12 Hz is observed in the lateral geniculate nucleus (LGN) of the lightly anesthetized cat. This paper describes a series of experiments in which the interactions between ongoing oscillatory potentials and periodic photic and electrical stimuli are analyzed using frequency domain techniques. The principal results of these experiments are consistent with a model of the neural system as an entrainable oscillator in which ongoing oscillations are suppressed by stimulation at nearby frequencies, but coexist with stimulus frequencies farther away. The physiological interpretation of these results may be closely tied to the role of the LGN as a gating mechanism between retina and cortex.Supported by NIH Training Grant #GM01455 and NSF Grant #ENG-7515736     

Light-induced responses of slow oscillatory neurons of the rat olivary pretectal nucleus

Background

The olivary pretectal nucleus (OPN) is a small midbrain structure responsible for pupil constriction in response to eye illumination. Previous electrophysiological studies have shown that OPN neurons code light intensity levels and therefore are called luminance detectors. Recently, we described an additional population of OPN neurons, characterized by a slow rhythmic pattern of action potentials in light-on conditions. Rhythmic patterns generated by these cells last for a period of approximately 2 minutes.

Methodology

To answer whether oscillatory OPN cells are light responsive and whether oscillatory activity depends on retinal afferents, we performed in vivo electrophysiology experiments on urethane anaesthetized Wistar rats. Extracellular recordings were combined with changes in light conditions (light-dark-light transitions), brief light stimulations of the contralateral eye (diverse illuminances) or intraocular injections of tetrodotoxin (TTX).

Conclusions

We found that oscillatory neurons were able to fire rhythmically in darkness and were responsive to eye illumination in a manner resembling that of luminance detectors. Their firing rate increased together with the strength of the light stimulation. In addition, during the train of light pulses, we observed two profiles of responses: oscillation-preserving and oscillation-disrupting, which occurred during low- and high-illuminance stimuli presentation respectively. Moreover, we have shown that contralateral retina inactivation eliminated oscillation and significantly reduced the firing rate of oscillatory cells. These results suggest that contralateral retinal innervation is crucial for the generation of an oscillatory pattern in addition to its role in driving responses to visual stimuli.     

Electrophysiology of the isolated central nervous system of the northern octopus Eledone cirrhosa

A successful preparation has been devised for maintaining the octopus brain in a viable condition to allow microelectrode studies of individual nerve cells. Impalements of cells within the sub‐oesophageal mass reveal that three populations of neurones are present These have different resting potentials, ranging from approximately 60 mV down to under 30 mV. Spontaneous activity is recorded from many neurones but some are silent and others exhibit only synaptic noise. Electrical stimulation of silent cells may lead to no response (large resting potential cells) or provoke trains of impulses (30–45 mV cells). Typical action potentials have durations of 20 msec. IPSP and EPSP activity may be observed. Burster cells or oscillators are located in one specific region, and a variety of activity may be recorded. These periodic bursts may be modified by hyperpolarisation so that spiking ceases but the underlying oscillatory potential remains. Some units exhibit two spike sizes, often uncorrelated in discharge.     

Reciprocal changes in center and surrounding S potentials of fish retina in response to dopamine

Effects of dopamine (DA) were examined on the intracellularly recorded potential from horizontal cells in the fish (Eugerres plumieri) retina. DA (100 M in the perfusate) augmented the center S potential in a response to a spot illumination and attenuated the surrounding S potential to an annular light by approximately 40%. These reciprocal changes in the S potentials were associated with a slight depolarization (2.5 mV) of the horizontal cell, and were reversible in 10–15 min. The results indicate that DA at this concentration does not affect directly the synaptic transmission from photoreceptors to horizontal cells, while it appears to interfere selectively with the lateral propagation of an S potential. The effects of DA observed may represent an aspect of function of DA-containing interplexiform cells in the retina.     

P2X<Subscript>7</Subscript>R modulation of visually evoked synaptic responses in the retina

P2X₇Rs are distributed throughout all layers of the retina, and thus, their localisation on various cell types puts into question their specific site(s) of action. Using a dark-adapted, ex vivo mouse retinal whole mount preparation, the present study aimed to characterise the effect of P2X₇R activation on light-evoked, excitatory RGC ON-field excitatory post-synaptic potentials (fEPSPs) and on outer retinal electroretinogram (ERG) responses under comparable conditions. The pharmacologically isolated NMDA receptor-mediated RGC ON-fEPSP was reduced in the presence of BzATP, an effect which was significantly attenuated by A438079 and other selective P2X₇R antagonists A804598 or AF27139. In physiological Krebs medium, BzATP induced a significant potentiation of the ERG a-wave, with a concomitant reduction in the b-wave and the power of the oscillatory potentials. Conversely, in the pharmacologically modified Mg²⁺-free perfusate, BzATP reduced both the a-wave and b-wave. The effects of BzATP on the ERG components were suppressed by A438079. A role for P2X₇R function in visual processing in both the inner and outer retina under physiological conditions remains controversial. The ON-fEPSP was significantly reduced in the presence of A804598 but not by A438079 or AF27139. Furthermore, A438079 did not have any effect on the ERG components in physiological Krebs but potentiated and reduced the a-wave and b-wave, respectively, when applied to the pharmacologically modified medium. Therefore, activation of P2X₇Rs affects the function in the retinal ON pathway. The presence of a high concentration of extracellular ATP would most likely contribute to the modulation of visual transmission in the retina in the pathophysiological microenvironment.     

Glutamate-induced K+ flux in the photoreceptor layer of isolated retina of cyprinid fish: possible consequences for second-order neurones

The effect of L-glutamate on extracellular K+ activity (aK0) in the micro-environment of the isolated retina of a cyprinid fish was investigated using double-barrelled K+-sensitive micro-electrodes. Glutamate was pulsed onto the retina from an atomizer, and aK0's recorded at different retinal depths. Glutamate induced a concentration-dependent rise in aK0 which was maximal in the first 100 microns of the retinal surface. The aK0 change was transient, with a time to peak of 20-30 s, and complete reversal within 4 min. However, if the retina was pre-treated with dinitrophenol or ouabain, the maximum rise in aK0 was greater than normal, and the effect was sustained. Application of equimolar glutamate transiently depolarized the membrane potentials of horizontal cells. The effects of glutamate on aK0 and horizontal cell membrane potential had some common characteristics. It is concluded that glutamate may have non-synaptic effects on post-receptoral retinal neurones, and possible mechanisms of this are considered.     

Loss of information on central summation of local postsynaptic potentials

The spatio-temporal pattern of spikes converging on a neuron and variations in the combined depolarizing potential in the trigger zone are regarded as information carriers. In both cases the quantity of information is calculated; it is assumed that the depolarizing potential is formed as the weighted sum of the local PSPs. It is concluded from a comparison of the results that "algebraic" summation of PSPs is accompained by loss of essential information, and information carried by variation in the combined PSP is generated only by unessential input information. The investigation confirms the important role of a high spatial damping constant of electrotonic potentials in the dendrites. The damping prevents annihilation of much of the information. Electrical action of "effective" synapses on the trigger zone must evidently be regarded as sensitivity control, with no effect on the information content of the process but capable of weakening or interrupting the transmission of information from dendrites to the trigger zone. It is concluded that the combined PSP cannot serve as an information carrier and that this function may perhaps be performed by signals of a different physical nature which do not undergo damping in the dendrites.M. I. Kalinin Leningrad Polytechnical Institute. Translated from Neirofiziologiya, Vol. 5, No. 2, pp. 186–192, March–April, 1973.     

Effects of the Intracellular Ca Ion Concentration upon the Excitability of the Muscle Fiber Membrane of a Barnacle

The membrane excitability and contraction were examined in single barnacle muscle fibers with different internal Ca⁺⁺ concentrations by using buffer solutions made up with EGTA and Ca-gluconate in various proportions. During the passage of dc currents the membrane shows all-or-none spike potentials for internal Ca⁺⁺ concentrations below about 8 x 10^-8 M, oscillatory potential changes in the range between 8 x 10^-8 to 5 x 10^-7 M, but neither oscillatory nor spike potentials were seen for concentrations above 5 x 10^-7 M. All-or-none spike potentials were suppressed when the internal Mg⁺⁺ concentration exceeded 5 mM. The suppression threshold of the internal Ca⁺⁺ concentration for the Sr spike is much higher than that for the Ca spike. The threshold concentration of internal Ca⁺⁺ for contraction was about 8 x 10^-7 M.     

In vivo recording of electrical activity of canine tracheal smooth muscle.

Electrical activity of the tracheal smooth muscle was studied using extracellular bipolar electrodes in 37 decerebrate, paralyzed, and mechanically ventilated dogs. A spontaneous oscillatory potential that consisted of a slow sinusoidal wave of 0.57 +/- 0.13 (SD) Hz mean frequency but lacked a fast spike component was recorded from 15 dogs. Lung collapse accomplished by bilateral pneumothoraxes evoked or augmented the slow potentials that were associated with an increase in tracheal muscle contraction in 26 dogs. This suggests that the inputs from the airway mechanoreceptors reflexly activate the tracheal smooth muscle cells. Bilateral vagal transection abolished both the spontaneous and the reflexly evoked slow waves and provided relaxation of the tracheal smooth muscle. Electrical stimulation of the distal nerve with a train pulse (0.5 ms, 1-30 Hz) evoked slow-wave oscillatory potentials accompanied by a contraction of the tracheal smooth muscle in all the experimental animals. Our observations in this in vivo study confirm that the electrical activity of tracheal smooth muscle consists of slow oscillatory potentials and that tracheal contraction is at least partly coupled to the slow-wave activity of the smooth muscle.     

Ontogenesis of the electroretinogram in a precocial mammal, the guinea pig (Cavia porcellus)

1. Ontogenesis of the electroretinogram, the mass electrical response of the retina to flash light stimuli, was studied in the guinea pig (Cavia porcellus), a precocial species with visual function at birth. 2. a-Wave components, b-wave, oscillatory potentials, slow PIII, and c-wave responses to flash stimuli developed between 55 and 64 days of gestation (full term is 68-69 days). 3. a-Waves attributable to photoreceptor functions were fully mature at 60 days. 4. ERG development lagged behind the reported critical milestones in retinal development; its prenatal onset indicates that no history of light entrainment is required for initiation of a mature ERG response.     

Electrophysiological organization of the eye of Aplysia

The eye of Aplysia californica was studied by electrophysiological and histological methods. It has a central spheroidal lens which is surrounded by a retina composed of several thousand receptor cells which are replete with clear vesicles, pigmented support cells, neurons which contain secretory granules, and glial cells. The thin optic nerve that connects the eye to the cerebral ganglion gives a simple "on" response of synchronized action potentials. Tonic activity occurs in the optic nerve in the dark and is dependent on previous dark adaptation. Micropipette recordings indicate that the ERG is positive (relative to a bathelectrode) on the outer surface of the eye and negative in the region of the distal segments of the receptors. Intracellular recordings show that receptor cells have resting potentials of 40–50 mv and respond to illumination with graded potentials of up to 55 mv. Dark-adapted receptors exhibit discrete bumps on the graded response to brief light flashes. Other elements in the retina that do not give large graded responses fall into two classes. One class responds to illumination with action potentials that are in synchrony with the extracellularly recorded compound optic nerve potentials. The other class is tonically active and is depolarized or hyperpolarized and inhibited upon illumination. It is apparent that complex excitatory and lateral inhibitory interactions occur among the elements of the retina.     

Ionic mechanism for the generation of horizontal cell potentials in isolated axolotl retina

The ionic mechanism of horizontal cell potentials was investigated in the isolated retina of the axolotl Ambystoma mexicanum. The membrane potentials of both receptors and horizontal cells were recorded intracellularly while the ionic composition of the medium flowing over the receptor side of the retina was changed. The membrane potential of the horizontal cell is highly depender side of the retina was changed. The membrane potential of the horizontal cell is highly dependent on the extracellular concentration of sodium. When the external ion concentration of either chloride or potassium was changed independently of the other, there were shifts in the membrane potential of the horizontal cell which could not be explained by changes in the equilibrium potential of these ions. If the external concentrations of both potassium and chloride ions were varied so that the product of their external concentrations did not change, the shift in the membrane potential of the horizontal cell was in the direction predicted by the Nernst equation. The results are consistent with the suggestion that in the dark the receptors release a synaptic transmitter which increases primarily the sodium conductance of the horizontal cell postsynaptic membrane.     

Cardiac pacemaker mechanisms in the ostracod crustacean Vargula hilgendorfii

The heart of the ostracod crustacean Vargula hilgendorfii has a single intrinsic neuron that morphologically appears to innervate the myocardium. We, therefore, examined the heart activity electrophysiologically to determine whether the heartbeat is neurogenic. Each heartbeat is associated with a myocardial action potential composed of a spike potential followed by a plateau potential. The frequency of the action potential is not stable but changes successively over a wide range. The action potential is not preceded by a pacemaker potential and has an inflection in its rising phase. The myocardial cells couple electrically and fire almost simultaneously. The frequency of the action potential was unchanged by injection of depolarizing or hyperpolarizing current into the myocardium. However, slow oscillatory potentials appeared during the depolarization and its frequency was higher with increasing current intensity. Application of 1-microM tetrodotoxin (TTX) depolarized the myocardial membrane and completely prevented the action potential. During this depolarization, slow oscillatory potentials often appeared spontaneously. These results suggest that, although the myocardium has a property of conditional oscillator, the heartbeat is driven by the single cell cardiac ganglion that has both pacemaker and motor functions.