scholarly journals A Mathematical Model for the Cardiac Action Potential Based on Slow Inactivation of Sodium Conductance

1968 ◽  
Vol 21 (1) ◽  
pp. 37 ◽  
Author(s):  
L Munk ◽  
E PGeorge
Keyword(s):  
Mathematical Model ◽  
Action Potential ◽  
Action Potentials ◽  
Sodium Current ◽  
Potassium Conductance ◽  
Slow Inactivation ◽  
Squid Axon ◽  
Purkinje Fibres ◽  
Cardiac Action ◽  
Potassium Conductances

A mathematical model for the action potential in Purkinje fibres is developed. It is based on voltage-clamp results which show that inactivation of sodium current in these muscles is much slower than in squid axon and that the latent rise in potassium conductance is not present. Both the sodium and the potassium conductances are represented as a sum of slow and fast components. This is incorporated in the suitably adjusted Hodgkin-Huxley model for the squid axon. It is shown that such a model can account satisfactorily for the shape of the action potentials in Purkinje fibres.

Dendrotoxin blocks accommodation in frog myelinated axons

1989 ◽  
Vol 62 (1) ◽  
pp. 174-184 ◽  
Author(s):  
M. O. Poulter ◽  
T. Hashiguchi ◽  
A. L. Padjen
Keyword(s):  
Action Potential ◽  
Computer Model ◽  
Action Potentials ◽  
Potassium Conductance ◽  
Constant Stimulus ◽  
Motor Axons ◽  
Myelinated Axons ◽  
Frequency Adaptation ◽  
Potassium Conductances ◽  
Slow Potassium

1. Intracellular microelectrode recordings from large sensory and motor myelinated axons in spinal roots of Rana pipiens were used to study the effects of dendrotoxin (DTX), a specific blocker of a fast activating potassium current (GKf1). 2. Dendrotoxin reduced the ability of myelinated sensory and motor axons to accommodate to a constant stimulus. A depolarizing current step, which normally evoked only one action potential, after dendrotoxin treatment (200-500 nM) produced a train of action potentials. These spike trains lasted 29 +/- 2.8 (SE) ms on average in sensory fibers (n = 18) and 40.2 +/- 4.5 ms in motor fibers (n = 9). 3. After dendrotoxin treatment, in addition to a reduction in the ability to accommodate to a constant stimulus, a slowing in the rate of action potential generation was evident (spike frequency adaptation). 4. Dendrotoxin had no effect on the rising phase of conducted action potentials evoked by peripheral stimulation. Together with a lack of effect on the absolute refractory period, these results indicate that dendrotoxin does not affect sodium channel activity. 5. The steady-state voltage/current relationship was unchanged in response to hyperpolarizing current pulses; however, there was a significant increase in cord resistance in response to depolarizing current steps, demonstrating that DTX decreases outward rectification. 6. A computer model based on Hodgkin and Huxley equations was developed, which included the three voltage-dependent potassium conductances described by Dubois. The model reproduced major experimental results: removal of the conductance, termed GKf1, reduced the accommodation in the early phase of a continuous stimulus, indicating that this current could be responsible for the early accommodation. The hypothesis that the slow potassium conductance GKs regulates late accommodation and action potential frequency adaptation is also supported by the computer model. 7. In summary, these results suggest that in amphibian myelinated sensory and motor axons, the activity of potassium conductances can account for accommodation and adaptation without involvement of sodium conductance activity.

scholarly journals Quantitative Description of Sodium and Potassium Currents and Computed Action Potentials in Myxicola Giant Axons

1973 ◽  
Vol 61 (3) ◽  
pp. 361-384 ◽  
Author(s):  
L. Goldman ◽  
C. L. Schauf
Keyword(s):  
Action Potentials ◽  
Initial Conditions ◽  
Sodium Current ◽  
Quantitative Description ◽  
Potassium Conductance ◽  
Giant Axons ◽  
Sodium Conductance ◽  
Potassium Conductances ◽  
The Right ◽  
Sodium And Potassium

All analysis of the sodium and potassium conductances of Myxicola giant axons was made in terms of the Hodgkin-Huxley m, n, and h variables. The potassium conductance is proportional to n2. In the presence of conditioning hyperpolarization, the delayed current translates to the right along the time axis. When this effect was about saturated, the potassium conductance was proportional to n3. The sodium conductance was described by assuming it proportional to m3h. There is a range of potentials for which τh and h∞ values fitted to the decay of the sodium conductance may be compared to those determined from the effects of conditioning pulses. τh values determined by the two methods do not agree. A comparison of h∞ values determined by the two methods indicated that the inactivation of the sodium current is not governed by the Hodgkin-Huxley h variable. Computer simulations show that action potentials, threshold, and subthreshold behavior could be accounted for without reference to data on the effects of initial conditions. However, recovery phenomena (refractoriness, repetitive discharges) could be accounted for only by reference to such data. It was concluded that the sodium conductance is not governed by the product of two independent first order variables.

Membrane Properties Related to the Firing Behavior of Zebrafish Motoneurons

2003 ◽  
Vol 89 (2) ◽  
pp. 657-664 ◽  
Author(s):  
Robert R. Buss ◽  
Charles W. Bourque ◽  
Pierre Drapeau
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Membrane Conductance ◽  
Membrane Properties ◽  
High Threshold ◽  
Calcium Dependent ◽  
Larval Zebrafish ◽  
Plateau Potential ◽  
Potassium Conductances ◽  
Action Potential Burst

The physiological and pharmacological properties of the motoneuron membrane and action potential were investigated in larval zebrafish using whole cell patch current-clamp recording techniques. Action potentials were eliminated in tetrodotoxin, repolarized by tetraethylammonium (TEA) and 3,4-diaminopyridine (3,4-AP)-sensitive potassium conductances, and had a cobalt-sensitive, high-threshold calcium component. Depolarizing current injection evoked a brief (approximately 10–30 ms) burst of action potentials that was terminated by strong, outwardly rectifying voltage-activated potassium and calcium-dependent conductances. In the presence of intracellular cesium ions, a prolonged plateau potential often followed brief depolarizations. During larval development (hatching to free-swimming), the resting membrane conductance increased in a population of motoneurons, which tended to reduce the apparent outward rectification of the membrane. The conductances contributing to action potential burst termination are hypothesized to play a role in patterning the synaptically driven motoneuron output in these rapidly swimming fish.

scholarly journals Action Potentials in Rhodnius Oocytes: Repolarization is Sensitive to Potassium Channel Blockers

1986 ◽  
Vol 126 (1) ◽  
pp. 119-132
Author(s):  
M. J. O'DONNELL
Keyword(s):  
Potassium Channel ◽  
Action Potentials ◽  
Potassium Conductance ◽  
Channel Blockers ◽  
Calcium Dependent ◽  
Outward Rectification ◽  
Current Voltage ◽  
Potassium Channel Blockers ◽  
Potassium Conductances ◽  
Voltage Dependent

Depolarization of Rhodnius oocytes evokes action potentials (APs) whose rising phase is calcium-dependent. The ionic basis for the repolarizing (i.e. falling) phase of the AP was examined. Addition of potassium channel blockers (tetraethylammonium, tetrabutylammonium, 4-aminopyridine, atropine) to the bathing saline increased the duration and overshoot of APs. Intracellular injection of tetraethyl ammonium had similar effects. These results suggest that a voltage-dependent potassium conductance normally contributes to repolarization. Repolarization does not require a chloride influx, because substitution of impermeant anions for chloride did not increase AP duration. AP duration and overshoot actually decreased progressively when chloride levels were reduced. Current/voltage curves show inward and outward rectification, properties often associated with potassium conductances. Outward rectification was largely blocked by external tetraethylammonium. Possible functions of the rectifying properties of the oocyte membrane are discussed.

Cl - channels in Chara

1982 ◽  
Vol 299 (1097) ◽  
pp. 435-445 ◽  
Keyword(s):  
Mathematical Model ◽  
Action Potential ◽  
Voltage Dependence ◽  
Quantitative Description ◽  
Chara Corallina ◽  
Squid Axon ◽  
Impedance Measurements ◽  
Time Constants ◽  
Effects Of Ph ◽  
Cl Channels

The action potential in the cells of the freshwater alga Chara corallina is slower than that in the nerve by about 1000-fold. The depolarization phase is brought on by the outflow of the Cl - ions. Voltage-clamp studies show that this Cl - current can be described by the Hodgkin-Huxley equations for the Na+ transient in the squid axon. The only change necessary to the form of the Hodgkin-Huxley equations is an introduction of a time delay between the stimulus and the onset of excitation. This mathematical model of the Chara action potential facilitates a quantitative description of the effects of pH and temperature. While a pH shift alters various Hodgkin-Huxley parameters, temperature change influences mainly the activation and inactivation time constants but leaves the voltage-dependence of these parameters unaffected. The delays in excitation are both temperature and potential dependent. In future some corrections to the Hodgkin-Huxley picture of the Chara action potential may be necessary, as recent impedance measurements suggest a change in the membrane capacitance at the time of excitation.

Multiple potassium conductances and their role in action potential repolarization and repetitive firing behavior of neonatal rat hypoglossal motoneurons

1993 ◽  
Vol 69 (6) ◽  
pp. 2150-2163 ◽  
Author(s):  
F. Viana ◽  
D. A. Bayliss ◽  
A. J. Berger
Keyword(s):  
Action Potential ◽  
Calcium Influx ◽  
Potassium Conductance ◽  
Firing Frequency ◽  
Neonatal Rat ◽  
Repetitive Firing ◽  
Firing Behavior ◽  
Hypoglossal Motoneurons ◽  
Potassium Conductances ◽  
Action Potential Repolarization

1. The role of multiple potassium conductances in action potential repolarization and repetitive firing behavior of hypoglossal motoneurons was investigated using intracellular recording techniques in a brain stem slice preparation of the neonatal rat (0-15 days old). 2. The action potential was followed by two distinct afterhyperpolarizations (AHPs). The early one was of short duration and is termed the fAHP; the later AHP was of longer duration and is termed the mAHP. The amplitudes of both AHPs were enhanced by membrane potential depolarization (further from EK). In addition, their amplitudes were reduced by high extracellular K+ concentration, suggesting that activation of potassium conductances underlies both phases of the AHP. 3. Prolongation of the action potential and blockade of the fAHP were observed after application of 1) tetraethylammonium (TEA) (1-10 mM) and 2) 4-aminopyridine (4-AP) (0.1-0.5 mM). Calcium channel blockers had little or no effect on the fAHP or action potential duration. 4. The size of the mAHP was diminished by 1) manganese, 2) lowering external Ca2+, 3) apamin, and 4) intracellular injection of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) suggesting that influx of calcium activates the potassium conductance that underlies the mAHP. 5. The mAHP was unaffected by nifedipine (20 microM), but was strongly reduced by focal application of omega-conotoxin GVIA, suggesting that N-type calcium channels represent the major calcium influx pathway for activation of the calcium-dependent K+ conductance underlying the mAHP. 6. Repetitive firing properties were investigated by injecting long-duration depolarizing current pulses. Steady-state firing rose linearly with injected current amplitude. The slope of the firing frequency-current (f-I) relationship averaged approximately 30 Hz/nA in control conditions. Blockade of the conductance underlying the mAHP caused a marked increase in the minimal repetitive firing frequency and in the slope of the f-I plot, indicating a prominent role for the conductance underlying the mAHP in controlling repetitive firing behavior. 7. We conclude that action potential repolarization and AHPs are due to activation of pharmacologically distinct potassium conductances. Whereas repolarization of the action potential and the fAHP involves primarily a voltage-dependent, calcium-independent potassium conductance that is TEA- and 4-AP-sensitive, the mAHP requires the influx of extracellular calcium and is apamin sensitive. Activation of the calcium-activated potassium conductance greatly influences the normal repetitive firing of neonatal hypoglossal motoneurons.

scholarly journals Two Components of the Cardiac Action Potential

1969 ◽  
Vol 54 (5) ◽  
pp. 607-635 ◽  
Author(s):  
Antonio Paes de Carvalho ◽  
Brian Francis Hoffman ◽  
Marilene de Paula Carvalho
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Time Course ◽  
Slow Component ◽  
Slow Inward Current ◽  
Equilibrium Potential ◽  
Slow Phase ◽  
Positive Equilibrium ◽  
Cardiac Action

Transmembrane potentials recorded from the rabbit heart in vitro were displayed as voltage against time (V, t display), and dV/dt against voltage (V, V or phase-plane display). Acetylcholine was applied to the recording site by means of a hydraulic system. Results showed that (a) differences in time course of action potential upstroke can be explained in terms of the relative magnitude of fast and slow phases of depolarization; (b) acetylcholine is capable of depressing the slow phase of depolarization as well as the plateau of the action potential; and (c) action potentials from nodal (SA and AV) cells seem to lack the initial fast phase. These results were construed to support a two-component hypothesis for cardiac electrogenesis. The hypothesis states that cardiac action potentials are composed of two distinct and physiologically separable "components" which result from discrete mechanisms. An initial fast component is a sodium spike similar to that of squid nerve. The slow component, which accounts for both a slow depolarization during phase 0 and the plateau, probably is dependent on the properties of a slow inward current having a positive equilibrium potential, coupled to a decrease in the resting potassium conductance. According to the hypothesis, SA and AV nodal action potentials are due entirely or almost entirely to the slow component and can therefore be expected to exhibit unique electrophysiological and pharmacological properties.

Depression of excitability by sphingosine 1-phosphate in rat ventricular myocytes

1998 ◽  
Vol 275 (6) ◽  
pp. H2291-H2299 ◽  
Author(s):  
Karen L. MacDonell ◽  
David L. Severson ◽  
Wayne R. Giles
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Sodium Current ◽  
Potassium Conductance ◽  
Ionic Currents ◽  
Stimulus Current ◽  
Muscle Action Potential ◽  
Action Potential Waveform ◽  
Sphingosine 1 Phosphate ◽  
Electrophysiological Effects

Sphingosine 1-phosphate (S-1- P) is a bioactive sphingolipid that is released from activated platelets. Extracellular S-1- P augments an inwardly rectifying potassium conductance in cultured atrial preparations, but the electrophysiological effects of this compound in the ventricle are unknown. The electrophysiological effects of S-1- P were examined in single myocytes from rat ventricular muscle. Action potential waveforms and underlying ionic currents in the presence and absence of 3 μM S-1- P (1–6 min) were recorded. S-1- P increased the minimum stimulus current needed to elicit an action potential by ∼100 pA. Pertussis toxin or preexposure to S-1- P did not alter this effect. The action potential waveform was unchanged by S-1- P. The inward sodium current ( I Na) was examined in a range of membrane potentials just negative to the potential for firing an action potential. S-1- P reversibly inhibited peak I Na by ∼50 pA, whereas the inward rectifier potassium current was not significantly changed. The results of this study suggest that S-1- P inhibits rat ventricular excitability by reducing I Na.

scholarly journals On the effects of divalent cations and ethylene glycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetate on action potential duration in frog heart.

1978 ◽  
Vol 71 (1) ◽  
pp. 47-67 ◽  
Author(s):  
D J Miller ◽  
A Mörchen
Keyword(s):  
Ethylene Glycol ◽  
Action Potential ◽  
Calcium Ions ◽  
Action Potentials ◽  
Time Course ◽  
Divalent Cations ◽  
Potassium Conductance ◽  
Resting Potential ◽  
Slow Inward Current ◽  
Frog Heart

Resting and action potentials were recorded from superfused strips of frog ventricle. Reducing the bathing calcium concentration ([Ca2+]0) with or without ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA) prolongs the action potential (AP). The change in the duration of the AP extends over many minutes, but is rapidly reversed by restoring calcium ions. Other changes (e.g., in resting potential and overshoot) are, however, only more slowly reversed. Reducing [Ca2+]0 with 0.2, 2, or 5 mM EGTA produces progressively greater prolongation of AP; maximum values were well in excess of 1 min. This prolongation can be reversed by other divalent cations in EGTA (Mg2+, Sr2+) or Ca-free (Mn2+) solutions, or by acetylcholine. Barium ions increase AP duration in keeping with their known effect on potassium conductance. D600, which blocks the slow inward current in cardiac muscle, is without effect on the action potentials recorded in EGTA solutions, or on the time course and extent of the recovery to normal duration upon restoring calcium ions. It is concluded that divalent cations exert an influence on membrane potassium conductance extracellularly in frog heart. The cell membrane does not become excessively "leaky" in EGTA solutions.

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