scholarly journals Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles

2016 ◽  
Vol 311 (3) ◽  
pp. H750-H758 ◽  
Author(s):  
Yasunori Kushiyama ◽  
Haruo Honjo ◽  
Ryoko Niwa ◽  
Hiroki Takanari ◽  
Masatoshi Yamazaki ◽  
...  
Keyword(s):  
Wave Length ◽  
Electrical Coupling ◽  
Spiral Wave ◽  
Resting Membrane Potential ◽  
Papillary Muscles ◽  
Linear Pattern ◽  
Electrotonic Interactions ◽  
Space Constant ◽  
Dose Dependent ◽  
Rotation Dynamics

It has been reported that blockade of the inward rectifier K+ current ( IK1) facilitates termination of ventricular fibrillation. We hypothesized that partial IK1 blockade destabilizes spiral wave (SW) re-entry, leading to its termination. Optical action potential (AP) signals were recorded from left ventricles of Langendorff-perfused rabbit hearts with endocardial cryoablation. The dynamics of SW re-entry were analyzed during ventricular tachycardia (VT), induced by cross-field stimulation. Intercellular electrical coupling in the myocardial tissue was evaluated by the space constant. In separate experiments, AP recordings were made using the microelectrode technique from right ventricular papillary muscles of rabbit hearts. Ba2+ (10–50 μM) caused a dose-dependent prolongation of VT cycle length and facilitated termination of VT in perfused hearts. Baseline VT was maintained by a stable rotor, where an SW rotated around an I-shaped functional block line (FBL). Ba2+ at 10 μM prolonged I-shaped FBL and phase-singularity trajectory, whereas Ba2+ at 50 μM transformed the SW rotation dynamics from a stable linear pattern to unstable circular/cycloidal meandering. The SW destabilization was not accompanied by SW breakup. Under constant pacing, Ba2+ caused a dose-dependent prolongation of APs, and Ba2+ at 50 μM decreased conduction velocity. In papillary muscles, Ba2+ at 50 μM depolarized the resting membrane potential. The space constant was increased by 50 μM Ba2+. Partial IK1 blockade destabilizes SW rotation dynamics through a combination of prolongation of the wave length, reduction of excitability, and enhancement of electrotonic interactions, which facilitates termination of ventricular tachyarrhythmias.

Effect of aminophylline on the contraction threshold of rat diaphragm fibers

1991 ◽  
Vol 71 (4) ◽  
pp. 1409-1414 ◽  
Author(s):  
A. S. Losavio ◽  
B. A. Kotsias
Keyword(s):  
Membrane Potential ◽  
Sarcoplasmic Reticulum ◽  
Resting Membrane Potential ◽  
Dependent Manner ◽  
Direct Visualization ◽  
Rat Diaphragm ◽  
Current Clamp ◽  
Cyclic Monophosphate ◽  
Dose Dependent

We studied the effect of aminophylline (0.1–1 mM) on the contraction threshold (CT) of rat diaphragm fibers (25 degrees C). The CT was measured by direct visualization (x200) of the fiber under current-clamp conditions. The main findings are the following: 1) Aminophylline lowers the CT, in a dose-dependent manner, toward more negative values of the resting membrane potential (Vm). 2) Dibutyryl adenosine 3′,5′-cyclic monophosphate (2 mM) shifts the CT, although this change is smaller than in the presence of xanthine. 3) Tetracaine (1 mM), a drug that diminishes Ca release from the sarcoplasmic reticulum, reduces the shift induced by 1 mM aminophylline; this is partially overcome by increasing aminophylline concentration to 5 mM. 4) Hyperpolarization of the fibers shifts the CT to more negative Vm. We suggest that the displacement in the CT to more negative Vm plays an important role in the potentiating effect of aminophylline. This could be the result of an enhancement of Ca release from the sarcoplasmic reticulum.

scholarly journals Phenanthrene impacts zebrafish cardiomyocyte excitability by inhibiting IKr and shortening action potential duration

2021 ◽  
Vol 153 (2) ◽  
Author(s):  
Shiva N. Kompella ◽  
Fabien Brette ◽  
Jules C. Hancox ◽  
Holly A. Shiels
Keyword(s):  
Air Pollution ◽  
Action Potential ◽  
Action Potential Duration ◽  
Cardiac Electrophysiology ◽  
Resting Membrane Potential ◽  
Dependent Manner ◽  
Polyaromatic Hydrocarbon ◽  
Premature Ventricular Contractions ◽  
Whole Cell Patch Clamp ◽  
Dose Dependent

Air pollution is an environmental hazard that is associated with cardiovascular dysfunction. Phenanthrene is a three-ringed polyaromatic hydrocarbon that is a significant component of air pollution and crude oil and has been shown to cause cardiac dysfunction in marine fishes. We investigated the cardiotoxic effects of phenanthrene in zebrafish (Danio rerio), an animal model relevant to human cardiac electrophysiology, using whole-cell patch-clamp of ventricular cardiomyocytes. First, we show that phenanthrene significantly shortened action potential duration without altering resting membrane potential or upstroke velocity (dV/dt). L-type Ca2+ current was significantly decreased by phenanthrene, consistent with the decrease in action potential duration. Phenanthrene blocked the hERG orthologue (zfERG) native current, IKr, and accelerated IKr deactivation kinetics in a dose-dependent manner. Furthermore, we show that phenanthrene significantly inhibits the protective IKr current envelope, elicited by a paired ventricular AP-like command waveform protocol. Phenanthrene had no effect on other IK. These findings demonstrate that exposure to phenanthrene shortens action potential duration, which may reduce refractoriness and increase susceptibility to certain arrhythmia triggers, such as premature ventricular contractions. These data also reveal a previously unrecognized mechanism of polyaromatic hydrocarbon cardiotoxicity on zfERG by accelerating deactivation and decreasing IKr protective current.

Hyperpolarizing effect of aminophylline, theophylline, and cAMP on rat diaphragm fibers

1988 ◽  
Vol 64 (5) ◽  
pp. 1893-1899 ◽  
Author(s):  
O. Delbono ◽  
B. A. Kotsias
Keyword(s):  
Normal Values ◽  
Bath Temperature ◽  
Resting Membrane Potential ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Rat Diaphragm ◽  
K Concentration ◽  
Dose Dependent ◽  
K Permeability

We studied the effect of aminophylline and theophylline (0.1–2 mM) on the resting membrane potential (Vm) of rat diaphragm fibers in vitro (25 degrees C). The main findings are the following. 1) Aminophylline and theophylline hyperpolarize the fibers in a dose-dependent manner. This effect is present with 0.1 and 0.25 mM of aminophylline and theophylline, respectively, and the maximum effect is reached with 1 mM of the drug (approximately 5–8 mV in comparison to the normal values). This effect is reversible by washing out the preparation with normal solution. 2) Dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP, 2 mM) produces a similar increment in the Vm. 3) The hyperpolarizing action observed in the presence of aminophylline, theophylline, and DBcAMP is suppressed by 5 X 10(-4) M ouabain or by lowering the bath temperature to 5 degrees C. These results suggest that the xanthines may directly or indirectly stimulate a Na-K pump. Two possibilities may be considered: 1) an electrogenic effect of the Na-K pump and 2) a reduction in the extracellular K+ concentration in the solution contacting the external side of the cell as a consequence of the activity of the Na-K pump. Alternative mechanisms such as a reduction in Na permeability or an increment in K permeability might collaborate in the hyperpolarizing effect of the drugs tested.

scholarly journals Ion Transport and Membrane Potential in CNS Myelinated Axons I. Normoxic Conditions

1997 ◽  
Vol 78 (4) ◽  
pp. 2086-2094 ◽  
Author(s):  
Lisa Leppanen ◽  
Peter K. Stys
Keyword(s):  
Membrane Potential ◽  
Optic Nerve ◽  
Ion Transport ◽  
Transport Systems ◽  
Resting Membrane Potential ◽  
High Dose ◽  
Myelinated Axons ◽  
Gap Technique ◽  
Influx Pathways ◽  
Dose Dependent

Leppanen, Lisa and Peter K. Stys. Ion transport and membrane potential in CNS myelinated axons. I. Normoxic conditions. J. Neurophysiol. 78: 2086–2094, 1997. Compound resting membrane potential was recorded by the grease gap technique during normoxic conditions (37°C) in rat optic nerve, a representative CNS myelinated tract. Mean potential was −47 ± 3 (SD) mV and remained stable for 2–3 h. Input impedance of a single optic nerve axon was calculated to be ≈5 GΩ. Contribution of the Na+ pump to resting axonal potential is estimated at −7 mV. Ouabain (10 μM to 10 mM) evoked a dose-dependent depolarization that was maximal at ≥1 mM, depolarizing the nerves to ∼35–40% of control after 60 min. Inhibiting energy metabolism (CN− and iodoacetate) during high-dose ouabain (1–10 mM) exposure caused an additional depolarization, suggesting additional ATP-dependent, ouabain-insensitive ion transport systems. Perfusion with zero-Na+ (choline substituted) caused a transient hyperpolarization, that was greater than with tetrodotoxin (TTX; 1 μM) alone, indicating both TTX-sensitive and -insensitive Na+ influx pathways in resting rat optic nerve axons. Resting probability (P)K:PNa is calculated at 20:1. In contrast to choline-substituted solution, Li+-substituted zero-Na+ perfusate caused a rapid depolarization due to Na+ pump inhibition and the ability of Li+ to permeate the Na+ channel. TTX reduced, but did not prevent, ouabain- or zero-Na+/Li+–induced depolarization. We conclude that the primary Na+ influx path in resting rat optic nerve axons is the TTX-sensitive Na+ channel, with evidence for additional TTX-insensitive routes permeable to Na+ and Li+. In addition, maintenance of membrane potential is critically dependent on continuous Na+ pump activity due to the relatively high exchange of Na+ (via the above mentioned routes) and K+ across the membrane of resting optic axons.

Electrotonic interactions between aggregates of chick embryo cardiac pacemaker cells

1986 ◽  
Vol 250 (3) ◽  
pp. H453-H463 ◽  
Author(s):  
R. D. Veenstra ◽  
R. L. DeHaan
Keyword(s):  
Electrical Coupling ◽  
Cardiac Pacemaker ◽  
Heart Cell ◽  
Embryonic Chick ◽  
Phase Resetting ◽  
Pacemaker Cells ◽  
Beat Rate ◽  
Electrotonic Interactions ◽  
External K

Synchronization of spontaneously active heart cell aggregates occurs shortly after they are brought into contact. The synchronous rate is determined by pacemaker phase resetting and passive subthreshold electrotonic interactions. To further study the effects of passive electrical interactions, we have used 150-microns diameter aggregates prepared from cells of 4d (4-day ventricle + 1 day in vitro), 7d, and 14d embryonic chick ventricle as models of primary, latent, and nonpacemaker tissues, respectively. Coupling of 4d and 7d aggregates (4d/7d pairs) leads to intermediate synchronous rates. We show here that elevating external K+ from 1.3 to 2.8 mM, which has no effect on 4d/4d pairs but selectively reduces the beat rate of 7d/7d pairs by 42%, slows the synchronous beat rate of 4d/7d pairs by 23%. Increases in electrical coupling in newly joined 4d/14d pairs cause the 4d rate to slow to a minimum value (16 +/- 13 beats/min, n = 16) just prior to the onset of synchronous activity. The rate slowly recovers to a final value of 40 +/- 12 beat/min. We conclude that the spontaneous beat rate of a primary pacemaker is modulated by both active and passive interactions with latent or nonpacemaker tissues.

scholarly journals Effect of presynaptic membrane potential on electrical vs. chemical synaptic transmission

2011 ◽  
Vol 106 (2) ◽  
pp. 680-689 ◽  
Author(s):  
Colin G. Evans ◽  
Bjoern Ch. Ludwar ◽  
Timothy Kang ◽  
Elizabeth C. Cropper
Keyword(s):  
Membrane Potential ◽  
Synaptic Transmission ◽  
Electrical Coupling ◽  
Mammalian Brain ◽  
Resting Membrane Potential ◽  
Presynaptic Membrane ◽  
Electrical Transmission ◽  
A Cell ◽  
Peripheral Activation ◽  
Chemical Transmission

The growing realization that electrical coupling is present in the mammalian brain has sparked renewed interest in determining its functional significance and contrasting it with chemical transmission. One question of interest is whether the two types of transmission can be selectively regulated, e.g., if a cell makes both types of connections can electrical transmission occur in the absence of chemical transmission? We explore this issue in an experimentally advantageous preparation. B21, the neuron we study, is an Aplysia sensory neuron involved in feeding that makes electrical and chemical connections with other identified cells. Previously we demonstrated that chemical synaptic transmission is membrane potential dependent. It occurs when B21 is centrally depolarized prior to and during peripheral activation, but does not occur if B21 is peripherally activated at its resting membrane potential. In this article we study effects of membrane potential on electrical transmission. We demonstrate that maximal potentiation occurs in different voltage ranges for the two types of transmission, with potentiation of electrical transmission occurring at more hyperpolarized potentials (i.e., requiring less central depolarization). Furthermore, we describe a physiologically relevant type of stimulus that induces both spiking and an envelope of depolarization in the somatic region of B21. This depolarization does not induce functional chemical synaptic transmission but is comparable to the depolarization needed to maximally potentiate electrical transmission. In this study we therefore characterize a situation in which electrical and chemical transmission can be selectively controlled by membrane potential.

scholarly journals Analytical Methods for Assessing Retinal Cell Coupling Using Cut-Loading

2021 ◽  
Author(s):  
William E. Myles ◽  
Sally Anne McFadden
Keyword(s):  
Electrical Coupling ◽  
Cell Types ◽  
Retinal Cell ◽  
Diffusion Method ◽  
Dye Transfer ◽  
Cell Coupling ◽  
Injection Techniques ◽  
Detailed Assessment ◽  
Space Constant ◽  
Different Populations

Abstract Electrical coupling between retinal neurons contributes to the functional complexity of visual circuits. “Cut-loading” methods allow simultaneous assessment of cell-coupling between multiple retinal cell-types, but existing analysis impedes direct comparison with gold standard direct dye injection techniques. Therefore cut-loading was used to assess coupling strength in a-type horizontal cells in dark-adapted Guinea pig retinae (n=29) using the standard protocol (Method 1) compared with two non-linear methods. Method 1 describes the distance of dye-diffusion (space constant), while Method 2 extracted the coupling coefficient (kj) and Method 3 measured the diffusion coefficient (De). Dye transfer was measured after one of five diffusion times (1-20 mins), or with a coupling inhibitor, meclofenamic acid (MFA) (50–500µM after 20 mins diffusion). Method 1 includes background fluorescence, producing less accurate coupling estimates than measuring the fluorescence of individual cell-soma (p<0.001). The space constant (Method 1) increased with diffusion time (p<0.01), whereas Methods 2 (p=0.54) and 3 (p=0.63) produced consistent results across all diffusion times. Method 1 was less sensitive to detecting changes induced by MFA than Methods 2 (p<0.01) and 3 (p<0.01). Comparatively, Methods 2 and 3 proved more sensitive and generalisable; allowing for detailed assessment of the coupling between different populations of gap-junction linked cell networks.

The self-propulsion of microscopic organisms through liquids

1953 ◽  
Vol 217 (1128) ◽  
pp. 96-121 ◽  
Keyword(s):  
Lateral Displacement ◽  
Wave Length ◽  
Plane Waves ◽  
Fluid Motion ◽  
Three Dimensional ◽  
Circular Cross Section ◽  
Spiral Wave ◽  
Small Radius ◽  
Inertial Forces ◽  
Single Wave

Since the Reynolds number of motion of microscopic organisms through liquids, defined as L ρ V /μ, where L is the length of the organism, V the velocity with which it moves, ρ the density of the liquid and μ the viscosity, is small, propulsion is due predominantly to the viscous forces, the effect of the inertial forces being negligible. The best-known problem that neglects all inertial forces is Stokes’s solution for the slow steady fluid motion past a sphere, in which the velocity field can be described in terms of singularities situated at the centre of the sphere. The movement of microscopic organisms is determined by placing distributions of these singularities inside the surface of the organism and satisfying all boundary conditions. The motions that are considered are restricted to organisms which propagate some kind of disturbance along filaments of circular cross-section with small radius. The first problem to be considered is that of an infinite thin filament along which are propagated plane waves of lateral displacement. Formulae for the velocity of propulsion are obtained for (i) the limiting case of zero radius and (ii) the case when the amplitude of the displacement is small compared to the wave-length. Computations have been carried out to estimate the propulsion in the case of small non-zero filament radius when the amplitude is larger than that allowed for in case (ii) above. It is also shown that the propulsion of a finite filament which forms itself into a single wave is very near to that of an infinite filament with the same wave motion. The second problem is that of an infinite filament along which any general three-dimensional disturbance is propagated. The movement is then deduced for the propagation of a spiral wave along an infinite filament, and also for the propagation of longitudinal waves along a finite filament.

Voltage-dependent action of tetrodotoxin in mammalian cardiac myocytes

1986 ◽  
Vol 251 (2) ◽  
pp. H475-H480
Author(s):  
P. M. Vassilev ◽  
R. W. Hadley ◽  
K. S. Lee ◽  
J. R. Hume
Keyword(s):  
Voltage Dependence ◽  
Ventricular Myocytes ◽  
Resting Membrane Potential ◽  
Na Channel ◽  
Patch Clamp Technique ◽  
Voltage Dependent ◽  
Channel Currents ◽  
Dose Dependent ◽  
Hyperpolarizing Shift ◽  
Channel Availability

Single Na+ channel currents have been examined in isolated guinea pig ventricular myocytes using the patch-clamp technique. The effects of lidocaine, extracellular calcium [(Ca)o], and tetrodotoxin on patch Na+ channel availability were assessed using ensemble averages of Na+-channel openings during depolarizing test potential steps from 7 to 10 different patch-holding potentials in each cell-attached patch. In six control patches, the potential for 50% channel availability (Vh) was -15 mV (relative to an average resting membrane potential of -80 mV). Exposure of patches to either lidocaine or elevated (Ca)o produced the expected shifts in Vh [average -22 mV for lidocaine and +10 mV for 6 mM (Ca)o]. Exposure of patches to tetrodotoxin (0.5 microM or 1.0 microM) produced a dose-dependent hyperpolarizing shift of Vh (average -10 and -17 mV) compared with control patches. The hyperpolarizing shift by tetrodotoxin was observed with pulses applied at frequencies of 1.0 or 0.067 Hz. In agreement with earlier maximal upstroke velocity studies in the same preparation, we conclude that block of ventricular Na+ channels by tetrodotoxin exhibits genuine steady-state voltage dependence.

scholarly journals Electrophysiological Properties of Rat Phrenic Motoneurons During Perinatal Development

1999 ◽  
Vol 81 (3) ◽  
pp. 1365-1378 ◽  
Author(s):  
Miguel Martin-Caraballo ◽  
John J. Greer
Keyword(s):  
Electrical Coupling ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Duration Of Action ◽  
Perinatal Development ◽  
Electrophysiological Properties ◽  
Calcium Dependent ◽  
Phrenic Motoneurons ◽  
Major Transformation ◽  
Afferent Terminals

Electrophysiological properties of rat phrenic motoneurons during perinatal development. Past studies determined that there is a critical period at approximately embryonic day (E)17 during which phrenic motoneurons (PMNs) undergo a number of pivotal developmental events, including the inception of functional recruitment via synaptic drive from medullary respiratory centers, contact with spinal afferent terminals, the completion of diaphragm innervation, and a major transformation of PMN morphology. The objective of this study was to test the hypothesis that there would be a marked maturation of motoneuron electrophysiological properties occurring in conjunction with these developmental processes. PMN properties were measured via whole cell patch recordings with a cervical slice–phrenic nerve preparation isolated from perinatal rats. From E16 to postnatal day 1, there was a considerable transformation in a number of motoneuron properties, including 1) 10-mV increase in the hyperpolarization of the resting membrane potential, 2) threefold reduction in the input resistance, 3) 12-mV increase in amplitude and 50% decrease duration of action potential, 4) major changes in the shapes of potassium- and calcium-mediated afterpotentials, 5) decline in the prominence of calcium-dependent rebound depolarizations, and 6) increases in rheobase current and steady-state firing rates. Electrical coupling among PMNs was detected in 15–25% of recordings at all ages studied. Collectively, these data and those from parallel studies of PMN–diaphragm ontogeny describe how a multitude of regulatory mechanisms operate in concert during the embryonic development of a single mammalian neuromuscular system.

Sign in / Sign up

Export Citation Format

Share Document