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Questioning the evidence for Earth's oldest fossils.

Structures resembling remarkably preserved bacterial and cyanobacterial microfossils from about 3,465-million-year-old Apex cherts of the Warrawoona Group in Western Australia currently provide the oldest morphological evidence for life on Earth and have been taken to support an early beginning for oxygen-producing photosynthesis. Eleven species of filamentous prokaryote, distinguished by shape and geometry, have been put forward as meeting the criteria required of authentic Archaean microfossils, and contrast with other microfossils dismissed as either unreliable or unreproducible. These structures are nearly a billion years older than putative cyanobacterial biomarkers, genomic arguments for cyanobacteria, an oxygenic atmosphere and any comparably diverse suite of microfossils. Here we report new research on the type and re-collected material, involving mapping, optical and electron microscopy, digital image analysis, micro-Raman spectroscopy and other geochemical techniques. We reinterpret the purported microfossil-like structure as secondary artefacts formed from amorphous graphite within multiple generations of metalliferous hydrothermal vein chert and volcanic glass. Although there is no support for primary biological morphology, a Fischer--Tropsch-type synthesis of carbon compounds and carbon isotopic fractionation is inferred for one of the oldest known hydrothermal systems on Earth.

Artifacts↗

Chromosome-level genome assembly and annotation of Petunia hybrida.

Petunia hybrida is the world's most popular garden plant and is regarded as a supermodel for studying the biology associated with the Asterid clade, the largest of the two major groups of flowering plants. Unlike other Solanaceae, petunia has a base chromosome number of seven, not 12. This along with recombination suppression has previously hindered efforts to assemble its genome to chromosome level. Here we achieve a chromosome-level assembly for P. hybrida using a combination of short-read and long-read sequencing, optical mapping (Bionano) and Hi-C technologies. The resulting assembly spans 1253.6 Mb with a BUSCO score of 99.8%. A total of 35,089 genes were predicted and of those 29,655 were functionally annotated. Syntenic regions between petunia, tomato and pepper were identified, highlighting rearrangements that have occurred since their divergence indicating that the 12 chromosomes of Solanaceae did not originate from whole genome duplication of an ancestral species with seven chromosomes like petunia. This assembly will enhance trait mapping efficiency and serve as a valuable resource for functional genomic studies.

Petunia↗

Role of wavelength adaptation in the initiation, maintenance, and pharmacologic suppression of reentry.

INTRODUCTION: The stability of reentry is thought to depend on a critical balance between the spatial extent of refractory tissue in a reentrant wave (i.e., wavelength lambda) and the reentrant path length. Because considerable evidence suggests that lambda changes continuously in space and time during abrupt rate changes associated with the onset of tachycardia, we hypothesized that beat-by-beat adaptation of A to the dimensions of the reentrant path plays a central role in the mechanism of initiation of reentry. METHODS AND RESULTS: To investigate the dynamic relationship between lambda and path length during initiation of reentry, optical mapping with voltage-sensitive dyes was used in a guinea pig model of reentrant ventricular tachycardia (VT). In this model, a computer-guided laser obstacle precisely controlled the position and dimensions of the reentrant path. Under control perfusion and after addition of 15 microM d-sotalol, lambda was monitored during steady-state pacing, premature stimulation, and the initiating beats leading to nonsustained and sustained VT. During control perfusion, reentrant VT was reproducibly induced in 8 of 8 hearts, whereas in the presence of d-sotalol, reentry could only be initiated in 1 of 8 hearts due primarily to the failure of lambda to adapt to the reentrant path length. During successful initiation of VT, a consistent sequence was observed. The sequence was characterized by antidromic and orthodromic propagation around both sides of the anatomic obstacle, followed by unidirectional block of the antidromic impulse and persistence of reentry only if the A of the orthodromic impulse adapted to the reentrant path (lambda < path length). d-Sotalol prevented initiation of VT by altering lambda adaptation of the orthodromic wave; however, it failed to terminate ongoing VT because reverse use-dependence developed after several beats of tachycardia. CONCLUSION: In an experimental model where lambda, path length, and cellular action potentials were monitored during initiation of reentry, we found that, in contrast to termination, the initiation of reentry and the transition from nonsustained to sustained VT is strongly dependent on beat-to-beat adaptation of lambda to the dimensions of the reentrant path.

Action Potentials↗

Theoretical and experimental study of sawtooth effect in isolated cardiac cell-pairs.

INTRODUCTION: The question of how a defibrillation shock affects the myocardium far (> approximately 1 mm; the space constant of continuum tissue models) from the electrode is not fully understood. According to a long-standing, yet to be verified, hypothesis, the relatively high-resistance intercellular gap junctions may help in coupling the shock effect to the distant myocardium by redistributing the defibrillation current and creating a sawtooth pattern of polarization in which every cell undergoes hyperpolarization and depolarization. The goal of this study was to conduct an in-depth theoretical and experimental investigation of the sawtooth effect in the simplest coupled system, that of an isolated cell-pair. METHODS AND RESULTS: Theoretically, we present a relationship between sawtooth amplitude (STA) and junctional resistance (Rj), and show that, in a cell-pair with two cells of different lengths, the sawtooth effect may not necessarily appear as a reversal in polarization across the junction when Rj is below a critical value. Experimentally, we optically mapped transmembrane potential responses along the lengths of enzymatically isolated guinea pig cell-pairs at 10- or 17-microm resolution, and estimated STA as the magnitude of discontinuity in responses at the intercellular junction. From 14 cell-pairs, STA was estimated to be approximately 11 mV for a nominal 10 V/cm field. Based on our theoretical results, this value corresponds to an Rj of approximately 18 Mohms. CONCLUSION: The intercellular junction induces a measurable sawtooth effect in the simplest system of an isolated cell-pair. An accounting for the sawtooth effect might be essential for understanding field-tissue interaction far from the electrode and to accurately predict tissue response during field stimulation.

Animals↗

Aging-related increase to inducible atrial fibrillation in the rat model.

INTRODUCTION: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging-related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging-related AF. METHODS AND RESULTS: Interatrial conduction time and atrial response to burst atrial pacing were evaluated in 11 young (2-3 months) and 12 old (22-24 months) male rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained (>30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12 old rats, respectively. No such arrhythmias could be induced in the young rats. Old rats had significantly (P < 0.01) longer interatrial conduction time and P wave durations than the young rats. Burst pacing failed to induce AT and AF in all 11 young rats studied. The effects of heptanol 2 to 10 microM were studied in both groups. Heptanol 2 to 5 microM promoted inducible AT in all 5 young rats studied; however, when its concentration was raised to 10 microM, AT could no longer be induced in any of the 5 young rats. No AF could be induced in any of the 5 young rats at heptanol concentrations of 2 to 10 microM. In the old rats, AF could still be induced during perfusion of 2 microM heptanol. However, when its concentration was raised to 5 and 10 microM, AF could not be induced in any of the 6 old rats studied. Optical mapping using a potentiometric dye showed a periodic single wavefront of activation during AT in both groups and 2 to 4 independent wavefronts propagating in different directions during AF in the old rats. Histology revealed a significant increase in interstitial atrial fibrosis (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young rats. Fibrosis in the old rats was highly heterogeneous. CONCLUSION: The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model.

Age Factors↗

Cellular mechanisms of vagally mediated atrial tachyarrhythmia in isolated arterially perfused canine right atria.

INTRODUCTION: Increased vagal tone significantly enhances susceptibility to atrial fibrillation (AF); however, the cellular mechanisms responsible for vagally mediated AF are not completely understood. METHODS AND RESULTS: In 12 isolated arterially perfused canine right atria, high-resolution optical mapping techniques were used to measure action potentials during control conditions, during intracardiac parasympathetic nerve stimulation (IPS; 30 to 50 Hz) as a surrogate for vagal stimulation, and during acetylcholine (ACh) infusion (10 to 30 microM). During steady-state pacing, action potential duration was shorter during ACh infusion (43 +/- 9 msec) than during IPS (78 +/- 7 msec, P < 0.001) or control (129 +/- 5 msec, P < 0.001). In contrast, repolarization gradients were larger during IPS (13 +/- 3 msec/mm) than during ACh infusion (3 +/- 1 msec/mm, P < 0.01) or control (5 +/- 1 msec/mm, P < 0.01). Transmural repolarization gradients were relatively small for each intervention tested. During ACh infusion, atrial tachyarrhythmia (AT) was easily initiated with a single premature stimulus and was associated with a focal pattern of activation (84%). AT also was easily initiated by a single premature stimulus during IPS; however, when repolarization gradients were large, patterns of conduction block and incomplete macroreentry were often observed (64%). Importantly, AT initiation during IPS was associated with focal activity (36%) when repolarization gradients were small. CONCLUSION: In contrast to ACh infusion, IPS generally increased dispersion of repolarization and was often associated with patterns of conduction block and incomplete macroreentry, similar to that associated with in vivo cervical vagal stimulation. However, IPS also was associated with a focal pattern of initiation that was independent of local repolarization gradients. These results suggest that during vagal stimulation, AT initiation does not always depend on repolarization gradients.

Acetylcholine↗

Delayed afterdepolarization inhibitor: a potential pharmacologic intervention to improve defibrillation efficacy.

INTRODUCTION: Electrical and optical mapping studies of defibrillation have demonstrated that following shocks of strength near the defibrillation threshold (DFT), the first several postshock cycles always arise focally. No immediate postshock reentry was observed. Delayed afterdepolarizations (DADs) have been suggested as a possible cause of this rapid repetitive postshock activity. The aim of this study was to test the hypothesis that DFT is decreased by application of a DAD inhibitor. METHODS AND RESULTS: Six pigs (30-35 kg) were studied. First, control DFT was determined using a three-reversal up/down protocol. Each shock (RV-SVC, biphasic, 6/4 msec) was delivered after 10 seconds of ventricular fibrillation (VF). Then, flunarizine (a DAD inhibitor) was injected intravenously (2 mg/kg bolus and 4 mg/kg/hour maintenance) and the DFT was again determined. A third DFT was determined 50 minutes after drug infusion was terminated to allow the drug to wash out. DFT after flunarizine application (520 +/- 90 V, 14 +/- 3 J) was significantly lower than control DFT (663 +/- 133 V, 23 +/- 4 J). After the drug washed out, DFT (653 +/- 107 V, 22 +/- 4 J) returned to the control DFT value (P = 0.6). Flunarizine reduced the DFT approximately 22% by leading-edge voltage and approximately 40% by energy. CONCLUSION: Flunarizine, a DAD inhibitor, significantly improved defibrillation efficacy. This finding suggests that DADs could be the source of the rapid repetitive focal activation cycles arising after failed near-DFT shocks before degeneration back into VF. Future studies are needed to investigate the cause of the earliest postshock activation and to determine if the DADs are responsible.

Animals↗

Effects of cytochalasin D on electrical restitution and the dynamics of ventricular fibrillation in isolated rabbit heart.

UNLABELLED: Cytochalasin D in Rabbit Ventricle. INTRODUCTION: Cytochalasin D (cyto-D) has been used as an excitation-contraction uncoupler during optical mapping studies. However, its effects on action potential duration restitution (APDR) and dynamics during ventricular fibrillation (VF) are unclear. METHODS AND RESULTS: Langendorff-perfused rabbit hearts (N = 6) were immersed in a tissue chamber. Transmembrane potential was recorded using glass microelectrodes. APD measured to 90% repolarization (APD90) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD90 (131 +/- 26 msec, 171 +/- 14 msec, and 177 +/- 14 msec) and steepened maximum slope of the APDR curve (1.1 +/- 0.2, 1.3 +/- 0.2, and 1.6 +/- 0.4 for control, 5 micromoles, and 10 micromoles, respectively; P < 0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD90, and steepened the maximum slope of the APDR curve. However, cyto-D did not significantly change the diastolic interval. The dominant frequency of pseudoelectrocardiogram progressively decreased with increasing concentrations of cyto-D (15.2 +/- 0.6 Hz, 11.1 +/- 2.4 Hz, and 9.8 +/- 3.2 Hz for control, 5 micromoles, and 10 micromoles, respectively; P < 0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 micromoles of cyto-D. CONCLUSION: Continuous perfusion of cyto-D at 5 or 10 micromoles prolonged APD90, steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.

Action Potentials↗

Coexistence of two types of ventricular fibrillation during acute regional ischemia in rabbit ventricle.

INTRODUCTION: We previously reported that a normal ventricle can demonstrate two types of ventricular fibrillation (VF), depending on the underlying electrophysiologic characteristics at the time of VF induction. We hypothesize that the two types of VF can coexist in acutely ischemic ventricles. METHODS AND RESULTS: Optical mapping studies were performed with di-4ANEPPS in 15 Langendorff-perfused rabbit hearts. Coronary artery branches were ligated to create regional ischemia in 10 hearts. Action potential duration measured to 50% repolarization (APD50) during ischemia showed an area with uniformly shortened APD50 (zone 1), an area with normal or lengthened APD50 (zone 3), and an area in between with an APD50 gradient (zone 2). Ischemia flattened APD restitution (APDR) slope and reduced conduction velocity in zone 1, creating a condition for type II VF. APDR steepened and the conduction velocity changed little in the nonischemic zone (zone 3), creating a condition for type I VF. During induced VF, the dominant frequency in zones 2 and 3 progressively increased after ischemia onset. The dominant frequency in zone 1 (ischemic zone) first decreased and then slightly increased but typically remained less than the dominant frequency in zone 3. The number of wavebreaks increased with time in all three zones (baseline: 4.3 +/- 1.5; 30 min: 11.7 +/- 5.6; 60 min: 15.6 +/- 11 per frame; P < 0.01). CONCLUSION: Two types of VF can coexist during acute regional ischemia. Both ischemic and nonischemic regions develop proarrhythmic changes during regional ischemia, thus contributing to increased ventricular vulnerability to VF and sudden death during acute coronary occlusion.

Analysis of Variance↗

Mechanism for atrial tachyarrhythmia in chronic volume overload-induced dilated atria.

UNLABELLED: Mechanism of chronic volume overload-induced AT. INTRODUCTION: Atrial dilatation associated with chronic volume overload (CVO) plays an important role in the development of atrial fibrillation (AF). However, the underlying mechanisms are unknown. METHODS AND RESULTS: CVO-induced atrial dilatation was created in Japanese white rabbits using arteriovenous shunt formation for 6 weeks. Epicardial action potentials were measured from both atria in Langendorff-perfused sham-operated control hearts (n=8) and in CVO hearts (n=8) using high-resolution optical mapping techniques. The left atrial diameter was greater in CVO hearts (16.0+/-0.4 mm) compared to control hearts (11.0+/-0.8 mm). During steady-state pacing, right and left atrial conduction velocities were significantly lower in CVO hearts compared to control hearts (P<0.01). Rapid atrial pacing did not induce atrial tachyarrhythmia (AT) in any control hearts. However, in seven of eight CVO hearts 16 episodes of AT were induced, of which 9 exhibited a single reentrant circuit. The remaining 7 episodes exhibited a focal pattern of excitation without evidence of reentry. Interestingly, the activation rate was higher during reentry (16.1+/-1.5 Hz) compared to focal AT (9.8+/-1.0 Hz). In addition, 15 of 16 episodes occurred in the posterior left atrium (PLA). In all seven CVO hearts, AT was self-sustained for more than 10 minutes. CONCLUSION: CVO caused atrial dilatation, conduction slowing, and AT associated with reentrant and focal excitation originating from the PLA. These results suggest that the PLA may play an important role in AT induction associated with CVO-induced atrial dilation.

Animals↗

Dissociation of membrane potential and intracellular calcium during ventricular fibrillation.

UNLABELLED: Membrane potential and intracellular calcium during VF. INTRODUCTION: The cardiac action potential (AP) and the intracellular Ca transient (CaT) are closely associated under normal physiological conditions, but not during ventricular fibrillation (VF). The purpose of this study was to determine whether this dissociation is directly related to the fast activation rate during VF. METHODS AND RESULTS: We optically mapped AP and CaT simultaneously in nine isolated rabbit hearts. Pinacidil, a K(ATP) channel opener, was used to shorten the action potential duration (APD) in order to capture tissue at fast pacing rates or to induce ventricular tachycardia (VT) comparable to VF activation rates. Mutual information (MI) was used to calculate the degree of AP and CaT coupling. Pinacidil (40 microM) infusion significantly shortened APD. The CL of VF without pinacidil averaged 77+/-13 ms, whereas the shortest CL achieved during VT under pinacidil infusion was 76 ms. MIs during fast pacing (1.13+/-0.15 bits) and fast VT (0.88+/-0.18 bits) were higher than those during baseline VF (0.39+/-0.11 bits), VF with pinacidil infusion (0.21+/-0.07 bits) and VF after pinacidil washout (0.36+/-0.15 bits). MIs during fast pacing or fast VT were higher than that of VFs at comparable dominant frequencies. CONCLUSIONS: CaT is closely associated with the AP during fast pacing and fast VT, but not during VF. The reduced MI during VF is not secondary to the fast rate of activation.

Animals↗

Delayed after depolarization-mediated triggered activity associated with slow calcium sequestration near the endocardium.

INTRODUCTION: Previously, we have shown that cells near the endocardium are more prone to elevated diastolic intracellular calcium levels than cells near the epicardium. The arrhythmogenic consequence of such regional differences in calcium handling is not clear. METHODS AND RESULTS: Using optical mapping techniques, calcium transients and action potentials were recorded simultaneously from ventricular sites across the transmural wall of the arterially perfused canine left ventricular wedge preparation during control conditions, and under conditions of increased calcium entry (I(K) blockade and beta-adrenergic stimulation). Under conditions of enhanced calcium entry, the decay of the calcium transient and diastolic calcium levels during rapid pacing were slower (38%, P < 0.01) and higher (215%, P < 0.02), respectively, near (within approximately 3 mm) the endocardium compared to the epicardium (n = 9). Immediately after termination of rapid pacing under conditions of increased calcium entry, ectopic activity and simultaneous delayed after depolarizations and spontaneous calcium release events were observed. Over all experiments, ectopic activity occurred more frequently closer to the endocardium compared to the epicardium. CONCLUSIONS: Under conditions of enhanced calcium entry, myocytes closer to the endocardium exhibit a higher level of diastolic calcium and greater ectopic activity compared to the epicardium. We show for the first time simultaneous delayed after depolarization and spontaneous calcium release events from myocytes in a normally coupled multicellular preparation. These data combined suggest that myocytes near the endocardium are more susceptible to calcium-mediated triggered activity.

Action Potentials↗

Sex modulates the arrhythmogenic substrate in prepubertal rabbit hearts with Long QT 2.

Females have a greater susceptibility to Torsade de Pointes in congenital and drug-induced long QT syndrome (LQTS) that has been attributed to the modulation of ion channel expression by sex hormones. However, little is known regarding sex differences in pre-puberty, that is, before the surge of sexual hormones. In patients with congenital LQTS types 1 and 2, male children tend to have a greater occurrence of adverse events, especially in 10-15 year olds, than their female counterpart. To evaluate whether the rabbit model of drug-acquired LQTS exhibits similar age dependences, hearts of prepubertal rabbits were perfused, mapped optically to record action potentials (APs) and treated with an I(Kr) blocker, E4031 to elicit LQTS2. As expected, AP durations (APD) were significantly longer in female (n = 18) than male hearts (n = 10), at long cycle length. Surprisingly, E4031 (50-250 nM) induced a greater prolongation of APDs in male than in female hearts, and in both genders reversed the direction of repolarization (apex --> base to base --> apex), enhancing dispersions of repolarization. Furthermore, in male hearts, E4031 (0.5 microM) elicited early afterdepolarizations (EADs) that progressed to polymorphic ventricular tachycardia (PVT) (n = 7/10) and were interrupted by isoproterenol (40 nM) and prevented by propranolol (0.5-2.5 microM). In female hearts, E4031 (0.5 microM) produced marked prolongations of APDs yet few EADs with no progression to PVT (n = 16/18). Thus, sex differences are opposite in prepubertal versus adult rabbits with respect to E4031-induced APD prolongation, EADs and PVT, underscoring the fact that APD prolongation alone is insufficient to predict arrhythmia susceptibility.

Action Potentials↗

Reduced intercellular coupling leads to paradoxical propagation across the Purkinje-ventricular junction and aberrant myocardial activation.

Ventricular tachycardia is a common heart rhythm disorder and a frequent cause of sudden cardiac death. Aberrant cell-cell coupling through gap junction channels, a process termed gap junction remodeling, is observed in many of the major forms of human heart disease and is associated with increased arrhythmic risk in both humans and in animal models. Genetically engineered mice with cardiac-restricted knockout of Connexin43, the major cardiac gap junctional protein, uniformly develop sudden cardiac death, although a detailed electrophysiological understanding of their profound arrhythmic propensity is unclear. Using voltage-sensitive dyes and high resolution optical mapping techniques, we found that uncoupling of the ventricular myocardium results in ectopic sites of ventricular activation. Our data indicate that this behavior reflects alterations in source-sink relationships and paradoxical conduction across normally quiescent Purkinje-ventricular muscle junctions. The aberrant activation profiles are associated with wavefront collisions, which in the setting of slow conduction may account for the highly arrhythmogenic behavior of Connexin43-deficient hearts. Thus, the extent of gap junction remodeling in diseased myocardium is a critical determinant of cardiac excitation patterns and arrhythmia susceptibility.

Animals↗

Sustained vortex-like waves in normal isolated ventricular muscle.

Sustained reentrant excitation may be initiated in small (20 x 20 x less than 0.6 mm) preparations of normal ventricular muscle. A single appropriately timed premature electrical stimulus applied perpendicularly to the wake of a propagating quasiplanar wavefront gives rise to circulation of self-sustaining excitation waves, which pivot at high frequency (5-7 Hz) around a relatively small "phaseless" region. Such a region develops only very low amplitude depolarizations. Once initiated, most episodes of reentrant activity last indefinitely but can be interrupted by the application of an appropriately timed electrical stimulus. The entire course of the electrical activity is visualized with high temporal and spatial resolution, as well as high signal-to-noise ratio, using voltage-sensitive dyes and optical mapping. Two- and three-dimensional graphics of the fluorescence changes recorded by a 10 x 10 photodiode array from a surface of 12 x 12 mm provide sequential images (every msec) of voltage distribution during a reentrant vortex. The results suggest that two-dimensional vortex-like reentry in cardiac muscle is analogous to spiral waves in other biological and chemical excitable media.

Animals↗

Electrical remodeling and arrhythmias in long-QT syndrome: lessons from genetic models in mice.

Mutations in cardiac voltage-gated K+ channels cause long-QT syndrome (LQTS) and sudden death. We have created a mouse with a long-QT phenotype by overexpression of truncated K+ channels in the heart and have investigated the phenotype of these mice. These mice have long-QT phenotype, and spontaneous and inducible arrhythmias. Optical mapping of Kv1DN mice revealed spatial and temporal dispersion of repolarization that underlies the arrhythmias. Here I review our attempts to abolish arrhythmias in this model by crossbreeding with Kv4DN and Kv2DN mice or direct injection of adenoviral or adeno-associated viral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the myocardium. Our published work suggests that the viral vectors rescue the phenotype at the cellular level, while crossbreeding with Kv4DN mice attenuates the spontaneous and inducible arrhythmias.

Action Potentials↗

Integration of local inputs in visual cortex.

In mammalian visual cortex, local connections are ubiquitous, extensively linking adjacent neurons of all types. In this study, optical maps of intrinsic signals and responses from single neurons were obtained from the same region of cat visual cortex while the effectiveness of the local cortical circuitry was altered by focally disinhibiting neurons within a column of known orientation preference. Maps of intrinsic signals indicated that local connections provide strong and functional subthreshold inputs to neighboring columns of other orientation preferences, altering the observed orientation preference to that of the disinhibited column. However, measuring the suprathreshold response using single-cell recordings revealed only mild changes of preferred orientation over the affected region. Because strongly tuned subthreshold inputs from cortex only marginally affect the tuning of a cortical cell's output, it is concluded that local cortical inputs are integrated weakly compared to geniculate inputs. Such circuitry potentially allows for the normalization of responses across a wide range of input activity through local averaging.

Animals↗

The effect of the cut surface during electrical stimulation of a cardiac wedge preparation.

Optical mapping from the cut surface of a "wedge preparation" allows observation inside the heart wall, below the epicardium or endocardium. We use numerical simulations based on the bidomain model to illustrate how the transmembrane potential is influenced by the cut surface. The distribution of transmembrane potential around a unipolar cathode depends on the fiber angle. For intermediate angles, hyperpolarization appears on only one side of the electrode, and is large and widespread.

Action Potentials↗