SIMPLE EXPERIMENTS TO UNDERSTAND THE IONIC ORIGINS AND CHARACTERISTICS OF THE VENTRICULAR CARDIAC ACTION POTENTIAL

2002 ◽  
Vol 26 (3) ◽  
pp. 185-194 ◽  
Author(s):  
Jean-Yves Le Guennec ◽  
Christophe Vandier ◽  
Gilles Bedfer
Keyword(s):  
Action Potential ◽  
Electrical Activity ◽  
Voltage Clamp ◽  
Undergraduate Students ◽  
Papillary Muscle ◽  
Action Potentials ◽  
Heart Function ◽  
Cardiac Action Potential ◽  
Extracellular Potassium ◽  
Cardiac Action

Electrophysiological experiments are helpful for students to understand the role of electrical activity in heart function. Papillary muscle, which belongs to the ventricle, offers the advantage of being easily studied using glass microelectrodes. In addition, there is commercially available software that simulates ventricular electrical activity and can help overcome some difficulties, such as voltage clamp experiments, which need expensive apparatus when used for studies on living preparations. Here, we present a class practical session that is taken by undergraduate students at our University. In the first part of this class, students record action potentials from papillary muscles with the use of glass microelectrodes, and they change extracellular conditions to study the ionic basis of the action potential. In the second part of the class, students simulate action potentials using the Oxsoft Heart model (v. 4.0) and model their previous experiments on papillary muscle to quantify the effects. In particular, the model is very helpful in promoting understanding of the effect that extracellular potassium has on cardiac action potential by simulating voltage clamp experiments. This twin approach of papillary muscle experiments and computer modeling leads to a good understanding of the functioning of the action potential and can help introduce discussion of some abnormal cardiac functioning.

AN ANALYSIS OF CONTROL OF THE VENTRICLE OF THE MOLLUSC MERCENARIA MERCENARIA

1993 ◽  
Vol 179 (1) ◽  
pp. 47-61
Author(s):  
C. L. Devlin
Keyword(s):  
Action Potential ◽  
Mercenaria Mercenaria ◽  
Lanthanum Chloride ◽  
Cardiac Action Potential ◽  
Extracellular Potassium ◽  
Plateau Phase ◽  
Progressive Reduction ◽  
Barium Ions ◽  
Cardiac Action ◽  
Ionophore Monensin

During spontaneous beating (autorhythmicity) in the bivalve ventricle, the cardiac action potential (AP) was generated by calcium (Ca2+) and sodium (Na+) influx. The initial fast rising phase (the ‘spike’) of the cardiac AP was dependent on extracellular Ca2+ concentration, whereas the slow plateau phase was Na+-dependent. The initial fast rising phase of the cardiac AP was abolished by treatment with a Ca2+-free saline or inorganic Ca2+ entry blockers, such as lanthanum chloride or cobalt. Conversely, this fast rising phase of the AP was potentiated by treatment with barium ions, the dihydropyridine-sensitive Ca2+ channel agonist Bay K 8644 or, unexpectedly, by the organic Ca2+ entry blocker diltiazem. The force of systolic beating was directly proportional to the amplitude of the fast rising phase of the cardiac AP. The Ca2+-dependent, fast rising phase of the AP was modulated by the level of extracellular Na+. Both the amplitude of the fast rising phase of the AP and coupled systolic force were increased by progressive reduction of extracellular Na+ concentration. The slow plateau phase was abolished by treatment with a Na+-free saline and potentiated by the Na+ ionophore monensin. The size of the Na+-dependent plateau was modulated by the level of extracellular Ca2+. When extracellular Ca2+ was removed from the bathing saline, both the amplitude and duration of the plateau phase were increased. Conversely, restoring extracellular Ca2+ to physiological levels decreased the size of the Na+-dependent plateau. Autorhythmicity was dependent on the level of extracellular potassium. In the absence of K+, neither a Ca2+-dependent fast rising phase nor a Na+-dependent plateau phase was recorded.

Effects of 5-Hydroxytryptamine on Action Potentials and on Contractile Force in the Ventricle of Dolabella Auricularia

1974 ◽  
Vol 61 (2) ◽  
pp. 529-539
Author(s):  
ROBERT B. HILL
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Entire Range ◽  
Contractile Force ◽  
Cardiac Action Potential ◽  
Force Of Contraction ◽  
Plateau Phase ◽  
Cardiac Action ◽  
Dolabella Auricularia

1. Concentrations of 5-hydroxytryptamine from 10-8 to 10-5M had the effect of starting quiescent ventricles, with a slow slight depolarization followed by the onset of beating, with hyperpolarization between beats. 2. Concentrations of 5-hydroxytryptamine from 10-7 to 10-3M had the effect of prolonging the cardiac action potential and increasing force. Over the entire range, an increase in concentration led to an increase in the duration and amplitude of the plateau phase of the action potential, and an increase in force of contraction.

Components of the cardiac action potential

1962 ◽  
Vol 203 (2) ◽  
pp. 258-260 ◽  
Author(s):  
T. Hoshiko ◽  
Nick Sperelakis
Keyword(s):  
Action Potential ◽  
Slow Wave ◽  
Action Potentials ◽  
The Other ◽  
Cardiac Action Potential ◽  
Intercalated Disc ◽  
Ringer’S Solution ◽  
Current Pulses ◽  
Cardiac Action ◽  
Intracellular Action

Two components have been observed in the intracellular action potentials of frog ventricular strips under conditions of impaired transmission. The strips were bathed in Ca-free, Mg Ringer's solution and were subjected to passage of current pulses through their length. Under these conditions a "notch" gradually developed at the beginning of the plateau and separated the action potential into a spike and a slow wave. In any given cell, the notch was often more prominent when the conditioned strip was stimulated from one end than from the other. Occasionally a spike in isolation spontaneously alternated with a spike plus slow wave response. The slow waves were generally graded in duration and magnitude with stimulus intensity or duration. The results are discussed in terms of a possible junctional response at the intercalated disc.

Contribution of Potassium Conductances to a Time-Dependent Transition in Electrical Properties of a Cockroach Motoneuron Soma

1999 ◽  
Vol 81 (5) ◽  
pp. 2253-2266 ◽  
Author(s):  
Janette D. Mills ◽  
Robert M. Pitman
Keyword(s):  
Electrical Properties ◽  
Action Potential ◽  
Electrical Activity ◽  
Voltage Clamp ◽  
Action Potentials ◽  
Time Dependent ◽  
K Channel ◽  
Plateau Potentials ◽  
Potassium Conductances ◽  
K Currents

Contribution of potassium conductances to a time-dependent transition in electrical properties of a cockroach motoneuron soma. The cell body of the cockroach ( Periplaneta americana) fast coxal depressor motoneuron (Df) displays a time-dependent change in excitability. Immediately after dissection, depolarization evokes plateau potentials, but after several hours all-or-none action potentials are evoked. Because K channel blockers have been shown to produce a similar transition in electrical properties, we have used current-clamp, voltage-clamp and action-potential-clamp recording to elucidate the contribution of different classes of K channel to the transition in electrical activity of the neuron. Apamin had no detectable effect on the neuron, but charybdotoxin (ChTX) caused a rapid transition from plateau potentials to spikes in the somatic response of Df to depolarization. In neurons that already produced spikes when depolarized, ChTX increased spike amplitude but did not increase their duration nor decrease the amplitude of their afterhyperpolarization. 4-Aminopyridine (4-AP) (which selectively blocks transient K currents) did not cause a transition from plateau potentials to spikes but did enhance oscillations superimposed on plateau potentials. When applied to neurons that already generated spikes when depolarized, 4-AP could augment spike amplitude, decrease the latency to the first spike, and prolong the afterhyperpolarization. Evidence suggests that the time-dependent transition in electrical properties of this motoneuron soma may result, at least in part, from a fall in calcium-dependent potassium current ( I K,Ca), consequent on a gradual reduction in [Ca2+ ]i. Voltage-clamp experiments demonstrated directly that outward K currents in this neuron do fall with a time course that could be significant in the transition of electrical properties. Voltage-clamp experiments also confirmed the ineffectiveness of apamin and showed that ChTX blocked most of I K,Ca. Application of Cd2+(0.5 mM), however, caused a small additional suppression in outward current. Calcium-insensitive outward currents could be divided into transient (4-AP-sensitive) and sustained components. The action-potential-clamp technique revealed that the ChTX-sensitive current underwent sufficient activation during the depolarizing phase of plateau potentials to enable it to shunt inward conductances. Although the ChTX-sensitive conductance apparently makes little contribution to spike repolarization, the ChTX-resistant I K,Ca does make a significant contribution to this phase of the action potential. The 4-AP-sensitive current began to develop during the rising phase of both action potentials and plateau potentials but had little effect on the electrical activity of the neuron, probably because of its relatively small amplitude.

scholarly journals Four ways to fit an ion channel model

2019 ◽  
Author(s):  
M. Clerx ◽  
K.A. Beattie ◽  
D.J. Gavaghan ◽  
G.R. Mirams
Keyword(s):  
Action Potential ◽  
Ion Channel ◽  
Voltage Clamp ◽  
Time Constant ◽  
Cardiac Action Potential ◽  
Channel Kinetics ◽  
Safety Critical ◽  
Independent Validation ◽  
Cardiac Action ◽  
Ion Channel Kinetics

ABSTRACTComputational models of the cardiac action potential are increasingly being used to investigate the effects of genetic mutations, predict pro-arrhythmic risk in drug development, and to guide clinical interventions. These safety-critical applications, and indeed our understanding of the cardiac action potential, depend on accurate characterisation of the underlying ionic currents. Four different methods can be found in the literature to fit ionic current models to single-cell measurements: (Method 1) fitting model equations directly to time constant, steady-state, and I-V summary curves; (Method 2) fitting by comparing simulated versions of these summary curves to their experimental counterparts; (Method 3) fitting to the current traces themselves from a range of protocols; and (Method 4) fitting to a single current trace from an information-rich voltage clamp protocol. We compare these methods using a set of experiments in which hERG1a current from single Chinese Hamster Ovary (CHO) cells was characterised using multiple fitting protocols and an independent validation protocol. We show that Methods 3 and 4 provide the best predictions on the independent validation set, and that the short information-rich protocols of Method 4 can replace much longer conventional protocols without loss of predictive ability. While data for Method 2 is most readily available from the literature, we find it performs poorly compared to Methods 3 and 4 both in accuracy of predictions and computational efficiency. Our results demonstrate how novel experimental and computational approaches can improve the quality of model predictions in safety-critical applications.Statement of SignificanceMathematical models have been constructed to capture and share our understanding of the kinetics of ion channel currents for almost 70 years, and hundreds of models have been developed, using a variety of techniques. We compare how well four of the main methods fit data, how reliable and efficient the process of fitting is, and how predictive the resulting models are for physiological situations. The most widely-used traditional approaches based on current-voltage and time constant-voltage curves do not produce the most predictive models. Short, optimised experimental voltage clamp protocols can be used to create models that are as predictive as ones derived from traditional protocols, opening up possibilities for measuring ion channel kinetics faster, more accurately and in single cells. As these models often form part of larger multi-scale action potential and tissue electrophysiology models, improved ion channel kinetics models could influence the findings of thousands of simulation studies.

scholarly journals Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current

2021 ◽  
Vol 22 (16) ◽  
pp. 8744
Author(s):  
Asfree Gwanyanya ◽  
Inga Andriulė ◽  
Bogdan M. Istrate ◽  
Farjana Easmin ◽  
Kanigula Mubagwa ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Voltage Clamp ◽  
Divalent Cation ◽  
Cardiac Myocyte ◽  
Cardiac Action Potential ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Cardiac Action ◽  
In Cells

The cardiac Mg2+-sensitive, TRPM6, and TRPM7-like channels remain undefined, especially with the uncertainty regarding TRPM6 expression in cardiomyocytes. Additionally, their contribution to the cardiac action potential (AP) profile is unclear. Immunofluorescence assays showed the expression of the TRPM6 and TRPM7 proteins in isolated pig atrial and ventricular cardiomyocytes, of which the expression was modulated by incubation in extracellular divalent cation-free conditions. In patch clamp studies of cells dialyzed with solutions containing zero intracellular Mg2+ concentration ([Mg2+]i) to activate the Mg2+-sensitive channels, raising extracellular [Mg2+] ([Mg2+]o) from the 0.9-mM baseline to 7.2 mM prolonged the AP duration (APD). In contrast, no such effect was observed in cells dialyzed with physiological [Mg2+]i. Under voltage clamp, in cells dialyzed with zero [Mg2+]i, depolarizing ramps induced an outward-rectifying current, which was suppressed by raising [Mg2+]o and was absent in cells dialyzed with physiological [Mg2+]i. In cells dialyzed with physiological [Mg2+]i, raising [Mg2+]o decreased the L-type Ca2+ current and the total delayed-rectifier current but had no effect on the APD. These results suggest a co-expression of the TRPM6 and TRPM7 proteins in cardiomyocytes, which are therefore the molecular candidates for the native cardiac Mg2+-sensitive channels, and also suggest that the cardiac Mg2+-sensitive current shortens the APD, with potential implications in arrhythmogenesis.

Effects of Acetylcholine on Resting and Action Potentials, and on Contractile Force in the Ventricle Of Dolabella Auricularia

1974 ◽  
Vol 61 (3) ◽  
pp. 629-637
Author(s):  
ROBERT B. HILL
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Cardiac Action Potential ◽  
Cardiac Action ◽  
Dolabella Auricularia ◽  
Isolated Ventricle

Acetylcholine (2x10-8 to 2x10-3 M depolarized the isolated ventricle of Dolabella auricularia. The depolarization was accompanied by a negatively inotropic effect from 2x10-8 M to 2x10-4 M, and by a positively tonotropic effect from 2x10-4 M to 2x10-3 M. The interaction of acetylcholine and 5-hydroxytryptamine was studied by artificially prolonging the plateau of the cardiac action potential by treatment with 5-HT. Acetylcholine had the effect of shortening the plateau established by 5-hydroxytryptamine. Force was reduced correspondingly.

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