scholarly journals Loading effect of fibroblast-myocyte coupling on resting potential, impulse propagation, and repolarization: insights from a microstructure model

2008 ◽  
Vol 294 (5) ◽  
pp. H2040-H2052 ◽  
Author(s):  
Vincent Jacquemet ◽  
Craig S. Henriquez
Keyword(s):  
Action Potential ◽  
Cardiac Cells ◽  
Resting Potential ◽  
Impulse Propagation ◽  
A Cell ◽  
Microstructure Model ◽  
Potential Impact ◽  
Electrical Connections ◽  
Fibroblast Density ◽  
Upstroke Velocity

The numerous nonmyocytes present within the myocardium may establish electrical connections with myocytes through gap junctions, formed naturally or as a result of a cell therapy. The strength of the coupling and its potential impact on action potential characteristics and conduction are not well understood. This study used computer simulation to investigate the load-induced electrophysiological consequences of the coupling of myocytes with fibroblasts, where the fibroblast resting potential, density, distribution, and coupling strength were varied. Conduction velocity (CV), upstroke velocity, and action potential duration (APD) were analyzed for longitudinal and transverse impulse propagation in a two-dimensional microstructure tissue model, developed to represent a monolayer culture of cardiac cells covered by a layer of fibroblasts. The results show that 1) at weak coupling (<0.25 nS), the myocyte resting potential was elevated, leading to CV up to 5% faster than control; 2) at intermediate coupling, the myocyte resting potential elevation saturated, whereas the current flowing from the myocyte to the fibroblast progressively slowed down both CV and upstroke velocity; 3) at strong couplings (>8 nS), all of the effects saturated; and 4) APD at 90% repolarization was usually prolonged by 0–20 ms (up to 60–80 ms for high fibroblast density and coupling) by the coupling to fibroblasts. The changes in APD depended on the fibroblast resting potential. This complex, coupling-dependent interaction of fibroblast and myocytes also has relevance to the integration of other nonmyocytes in the heart, such as those used in cellular therapies.

Helping students to understand that outward currents depolarize cells.

1999 ◽  
Vol 276 (6) ◽  
pp. S62
Author(s):  
M Stewart
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Building Blocks ◽  
Resting Potential ◽  
Potassium Ions ◽  
General Statement ◽  
Outward Currents ◽  
Excitable Membranes ◽  
A Cell

The physiology of excitable membranes is a fundamental topic in neuroscience and physiology courses at graduate and undergraduate levels. From the building blocks of ionic gradients and membrane channels whose permeability is selective and variable, we build the concepts of resting potential, action potential, and propagation in neurons and muscle fibers. Many students have an intuitive understanding of the movements of ions and the associated changes in membrane potential. For example, potassium ions leaving a cell through potassium-selective channels become unbalanced positive charges on the outside of the cell (and leave unbalanced negative charges on the inside), thus producing a potential across the membrane with the inside negative with respect to the outside. Later, when we discuss the local circuit currents that underlie propagation or the basis for extracellular stimulation, we make the general statement that "outward currents depolarize cells." Students respond with utter disbelief. Two simple additions to a discussion of membranes are suggested that permit the formulation of a consistent set of rules that apply to everything from the resting and action potentials of nerve and muscle through synaptic potentials and stimulation techniques.

Effect of high K, low K, and quinidine on QRS duration and ventricular action potential

1962 ◽  
Vol 203 (6) ◽  
pp. 1135-1140 ◽  
Author(s):  
Leonard S. Gettes ◽  
Borys Surawicz ◽  
James C. Shiue
Keyword(s):  
Action Potential ◽  
Resting Potential ◽  
Qrs Complex ◽  
High Potassium ◽  
Conduction Disturbances ◽  
High K ◽  
Low Potassium ◽  
Qrs Duration ◽  
Low K ◽  
Upstroke Velocity

Perfusion of isolated rabbit hearts with high potassium, low potassium, and quinidine solutions caused a diffuse widening of the QRS complex with no change in shape. These QRS changes were correlated with the magnitude and upstroke velocity of the ventricular transmembrane potential. An increase of QRS duration by 132% produced by high K was accompanied by a decrease of the action potential, resting potential, and upstroke velocity. A similar increase in QRS duration produced by quinidine was accompanied by a slow upstroke velocity but no change in magnitude of the action potential or resting potential. An increase of QRS duration by 49% produced by low K was accompanied by an increased action and resting potential, and upstroke velocity. We attributed the QRS changes produced by high K and quinidine, at least partly, to a slow conduction in the ventricle, caused by a slow upstroke velocity of the action potential. The QRS changes produced by low K could be explained by hyperpolarization. Early arrhythmias caused by low K were due to atrioventricular conduction disturbances.

Membrane Potentials in Normal, Isolated, Perfused Frog Hearts

1957 ◽  
Vol 190 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Frederick Ware ◽  
A. L. Bennett ◽  
A. R. McIntyre
Keyword(s):  
Action Potential ◽  
Graphical Method ◽  
Membrane Potentials ◽  
Resting Potential ◽  
Perfusion Fluid ◽  
Time Curve ◽  
Oscilloscope Trace ◽  
Average Maximum ◽  
Cathode Follower ◽  
Upstroke Velocity

Intracellular potentials from isolated normal frog hearts were measured in a series of 29 experiments, using microelectrodes of less than 1 micron tip diameter, a cathode follower input, direct coupled amplifier, and photographic registration of an oscilloscope trace. The perfusion fluid was Clark's solution, containing 1.08 mm calcium and 1.88 mm potassium. The average of 485 measurements of the normal resting potential was 84.5 mv. The average of 421 measurements of overshoot was 18.9 mv; and the average of 421 measurements of action potential was 102.5 mv. In eight experiments, including 141 values, the maximum depolarization rate was determined, using a graphical method of analysis. The average maximum upstroke velocity was 33.9 v/sec. The voltage-time curve of the action potential during the repolarization sequence showed considerable variation from fiber to fiber, but in most cases some evidence of a ‘spike’ component was seen.

scholarly journals A novel inward-rectifying K+ current with a cell-cycle dependence governs the resting potential of mammalian neuroblastoma cells.

1995 ◽  
Vol 489 (2) ◽  
pp. 455-471 ◽  
Author(s):  
A Arcangeli ◽  
L Bianchi ◽  
A Becchetti ◽  
L Faravelli ◽  
M Coronnello ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Neuroblastoma Cells ◽  
Resting Potential ◽  
K Current ◽  
A Cell ◽  
Cell Cycle Dependence ◽  
Cycle Dependence

Electrophysiology of the Giant Nerve Cell Bodies of Limnaea Stagnalis (L.) (Gastropoda: Pulmonata)

1974 ◽  
Vol 60 (3) ◽  
pp. 653-671
Author(s):  
D. B. SATTELLE
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Cell Types ◽  
Resting Potential ◽  
Constant Field ◽  
Bathing Medium ◽  
Mean Values ◽  
Relative Contribution ◽  
External Potassium ◽  
Limnaea Stagnalis

1. A mean resting potential of -53.3 (S.D. ±2.7) mV has been obtained for 23 neurones of the parietal and visceral ganglia of Limnaea stagnalis (L.). Changes in the resting potential of between 28 and 43 mV accompany tenfold changes in [K+0]. A modified constant-field equation accounts for the behaviour of most cells over the range of external potassium concentrations from 0-5 to 10.o mM/1. Mean values have been estimated for [K+1, 56.2 (S.D.± 9-0) mM/1 and PNa/PK, 0-117 (S.D.±0-028). 2. Investigations on the ionic basis of action potential generation have revealed two cell types which can be distinguished according to the behaviour of their action potentials in sodium-free Ringer. Sodium-sensitive cells are unable to support action potentials for more than 8-10 min in the absence of sodium. Sodium slopes of between 29 and 37 mV per decade change in [Na+0] have been found for these cells. Tetrodotoxin (5 x 10-5 M) usually blocks action potentials in these neurones. Calcium-free inger produces a marked reduction in the overshoot potential and calcium slopes of about 18 mV per decade change in [Ca2+o] are found. Manganous chloride only partially reduces the action potential overshoot in these cells at concentrations of 10 mM/l. 3. Sodium-insensitive neurones maintain action potentials in the absence of external sodium. Stimulation only slightly reduces the amplitude of the action potential under these conditions and such cells are readily accessible to potassium ions in the bathing medium. A calcium-slope of 29 mV per decade change in [Ca2+o] has been observed in these cells in the absence of external sodium. 4. It is concluded that both sodium and calcium ions can be involved in the generation of the action potential in neurones of Limnaea stagnate, their relative contribution varying in different cells.

Mechanisms and Physiological Implications of Cooperative Gating of Ion Channels Clusters

2021 ◽  
Author(s):  
Rose Ellen Dixon ◽  
Manuel F. Navedo ◽  
Marc D Binder ◽  
L. Fernando Santana
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Transient Receptor Potential ◽  
Imaging Techniques ◽  
Ryanodine Receptors ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Cardiac Cells ◽  
Fine Tuning ◽  
Voltage Gated

Ion channels play a central role in the regulation of nearly every cellular process. Dating back to the classic 1952 Hodgkin-Huxley model of the generation of the action potential, ion channels have always been thought of as independent agents. A myriad of recent experimental findings exploiting advances in electrophysiology, structural biology, and imaging techniques, however, have posed a serious challenge to this long-held axiom as several classes of ion channels appear to open and close in a coordinated, cooperative manner. Ion channel cooperativity ranges from variable-sized oligomeric cooperative gating in voltage-gated, dihydropyridine-sensitive Cav1.2 and Cav1.3 channels to obligatory dimeric assembly and gating of voltage-gated Nav1.5 channels. Potassium channels, transient receptor potential channels, hyperpolarization cyclic nucleotide-activated channels, ryanodine receptors (RyRs), and inositol trisphosphate receptors (IP3Rs) have also been shown to gate cooperatively. The implications of cooperative gating of these ion channels range from fine tuning excitation-contraction coupling in muscle cells to regulating cardiac function and vascular tone, to modulation of action potential and conduction velocity in neurons and cardiac cells, and to control of pace-making activity in the heart. In this review, we discuss the mechanisms leading to cooperative gating of ion channels, their physiological consequences and how alterations in cooperative gating of ion channels may induce a range of clinically significant pathologies.

Form follows function: how muscle shape is regulated by work

2000 ◽  
Vol 88 (3) ◽  
pp. 1127-1132 ◽  
Author(s):  
Brenda Russell ◽  
Delara Motlagh ◽  
William W. Ashley
Keyword(s):  
Muscle Cell ◽  
Cell Shape ◽  
Force Production ◽  
Cardiac Cells ◽  
Cross Sectional Area ◽  
Dynamic Responses ◽  
Mechanical Activity ◽  
Sectional Area ◽  
Cross Sectional ◽  
A Cell

What determines the shape, size, and force output of cardiac and skeletal muscle? Chicago architect Louis Sullivan (1856–1924), father of the skyscraper, observed that “form follows function.” This is as true for the structural elements of a striated muscle cell as it is for the architectural features of a building. Function is a critical evolutionary determinant, not form. To survive, the animal has evolved muscles with the capacity for dynamic responses to altered functional demand. For example, work against an increased load leads to increased mass and cross-sectional area (hypertrophy), which is directly proportional to an increased potential for force production. Thus a cell has the capacity to alter its shape as well as its volume in response to a need for altered force production. Muscle function relies primarily on an organized assembly of contractile and other sarcomeric proteins. From analysis of homogenized cells and molecular and biochemical assays, we have learned about transcription, translation, and posttranslational processes that underlie protein synthesis but still have done little in addressing the important questions of shape or regional cell growth. Skeletal muscles only grow in length as the bones grow; therefore, most studies of adult hypertrophy really only involve increased cross-sectional area. The heart chamber, however, can extend in both longitudinal and transverse directions, and cardiac cells can grow in length and width. We know little about the regulation of these directional processes that appear as a cell gets larger with hypertrophy or smaller with atrophy. This review gives a brief overview of the regulation of cell shape and the composition and aggregation of contractile proteins into filaments, the sarcomere, and myofibrils. We examine how mechanical activity regulates the turnover and exchange of contraction proteins. Finally, we suggest what kinds of experiments are needed to answer these fundamental questions about the regulation of muscle cell shape.

Osmotic effects on the CA1 neuronal population in hippocampal slices with special reference to glucose

1991 ◽  
Vol 65 (5) ◽  
pp. 1055-1066 ◽  
Author(s):  
B. A. Ballyk ◽  
S. J. Quackenbush ◽  
R. D. Andrew
Keyword(s):  
Action Potential ◽  
Single Cell ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Stratum Radiatum ◽  
Resting Potential ◽  
Excitatory Postsynaptic Potential ◽  
Stratum Pyramidale ◽  
Postsynaptic Potential ◽  
Axonal Excitability

1. Lowered osmolality promotes epileptiform activity both clinically and in the hippocampal slice preparation, but it is unclear how neurons are excited. We studied the effects of altered osmolality on the electrophysiological properties of CA1 pyramidal cells in hippocampal slices by the use of field and intracellular recordings. The excitability of these neurons under various osmotic conditions was gauged by population spike (PS) amplitude, single cell properties, and evoked synaptic input. 2. The orthodromic PS recorded in stratum pyramidale and the field excitatory postsynaptic potential (EPSP) in stratum radiatum were inversely proportional in amplitude to the artificial cerebrospinal fluid (ACSF) osmolality over a range of +/- 80 milliosmoles/kgH2O (mosM). The effect was osmotic because changes occurred within the time frame expected for cellular expansion or shrinkage and because permeable substances such as dimethyl sulfoxide or glycerol were without effect. Dilutional changes in ACSF constituents were experimentally ruled out as promoting excitability. 3. To test whether the field data resulted from a change in single-cell excitability, CA1 cells were intracellularly recorded during exposure to +/- 40 mosM ACSF over 15 min. There was no consistent effect upon CA1 resting potential, cell input resistance, or action potential threshold. 4. Osmotic alteration of orthodromic and antidromic field potentials might involve a change in axonal excitability. However, the evoked afferent volley recorded in CA1 stratum pyramidale or radiatum, which represents the compound action potential (CAP) generated in presynaptic axons, remained osmotically unresponsive with regard to amplitude, duration, or latency. This was also characteristic of CAPs evoked in isolated sciatic and vagus nerve preparations exposed to +/- 80 mosM. Therefore axonal excitability and associated extracellular current flow generated periaxonally are not significantly affected by osmotic shifts. 5. The osmotic effect on field potential amplitudes appeared to be independent of synaptic transmission because the inverse relationship with osmolality held for the antidromically evoked PS. Moreover, as recorded with respect to ground, the intracellular EPSP-inhibitory postsynaptic potential (IPSP) sequence (evoked from CA3 stratum radiatum) was not altered by osmolality. 6. The PS could occasionally be recorded intracellularly as a brief negativity interrupting the evoked EPSP. In hyposmotic ACSF, the amplitude increased and action potentials arose from the trough of the negativity as expected for a field effect. This is presumably the result of enhanced intracellular channeling of current caused by the increased extracellular resistance that accompanies cellular swelling.(ABSTRACT TRUNCATED AT 400 WORDS)

Dichotomy of Action-Potential Backpropagation in CA1 Pyramidal Neuron Dendrites

2001 ◽  
Vol 86 (6) ◽  
pp. 2998-3010 ◽  
Author(s):  
Nace L. Golding ◽  
William L. Kath ◽  
Nelson Spruston
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Resting Potential ◽  
Model Parameters ◽  
Voltage Sensitivity ◽  
Whole Cell ◽  
Ca1 Pyramidal Neurons ◽  
Whole Cell Recordings

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 μm from the soma, single backpropagating action potentials exhibit <50% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 μm from the soma, action potentials in most cells backpropagated either strongly (26–42% attenuation; n = 9/20) or weakly (71–87% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300–410 μm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.

Persistence of the electrophysiologic effects of mexiletine in canine Purkinje fibers alters the response to subsequent hypoxia

1987 ◽  
Vol 65 (10) ◽  
pp. 2104-2109
Author(s):  
Neil D. Berman ◽  
Richard I. Ogilvie ◽  
James E. Loukides
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Free Solution ◽  
Purkinje Fibers ◽  
Subsequent Exposure ◽  
Hydrochloride Solution ◽  
Drug Free ◽  
Microelectrode Techniques ◽  
Upstroke Velocity ◽  
Normal Formula

The persistence of cellular electropharmacologic effects of mexiletine on canine Purkinje fibers was studied utilizing standard microelectrode techniques and two different protocols. In the first, the tissue was exposed to hypoxic perfusion before and 30 min after perfusion with one of the following: mexiletine hydrochloride 6.25 μM solution, mexiletine hydrochloride 12.5 μM solution, or drug-free Tyrode's solution. With the higher concentration of mexiletine, depression of the maximal upstroke velocity [Formula: see text] persisted 30 min after drug washout and subsequent exposure to hypoxia did not result in the anticipated shortening of action potential duration but did prevent the restoration of normal [Formula: see text]. After perfusion with the lower concentration of mexiletine, [Formula: see text] was not depressed and hypoxic action potential duration shortening was not prevented. In the second protocol, Purkinje fibers were perfused with 12.5 μM mexiletine hydrochloride solution and then exposed to hypoxia after 15, 30,45, or 60 min of perfusion with drug-free solution. Depression of maximal upstroke velocity and shortening of action potential duration persisted during washout, returning to control values by 45 min, although mexiletine was not detectable in the tissue bath after 10 min of washout. Hypoxia initiated at 15 or 30 min of washout failed to produce the anticipated shortening of action potential duration. At 45 and 60 min, action potential duration was shortened by hypoxia. We concluded that mexiletine depression of [Formula: see text] and shortening of action potential duration may persist in the absence of drug. Further shortening of action potential duration in response to hypoxia is prevented during this period. The persistence of [Formula: see text] depression is prolonged by hypoxia.

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