Cardiac Pacemaker Activity: From Single Cells to Modelling the Heart

1993 ◽  
pp. 93-110
Author(s):  
D. Noble ◽  
J.C. Denyer ◽  
H.F. Brown ◽  
R. Winslow ◽  
A. Kimball
Keyword(s):  
Single Cells ◽  
Cardiac Pacemaker ◽  
Pacemaker Activity

scholarly journals Disease-associated HCN4 V759I variant is not sufficient to impair cardiac pacemaking

2020 ◽  
Vol 472 (12) ◽  
pp. 1733-1742
Author(s):  
Nadine Erlenhardt ◽  
Olaf Kletke ◽  
Franziska Wohlfarth ◽  
Marlene A. Komadowski ◽  
Lukas Clasen ◽  
...  
Keyword(s):  
Family History ◽  
Sick Sinus Syndrome ◽  
Cardiac Pacemaker ◽  
Cell Surface Expression ◽  
Pacemaker Activity ◽  
Hcn Channel ◽  
Functional Interpretation ◽  
Rat Cardiomyocytes ◽  
Cardiac Pacemaking ◽  
History Of

AbstractThe hyperpolarization-activated cation current If is a key determinant for cardiac pacemaker activity. It is conducted by subunits of the hyperpolarization-activated cyclic nucleotide–gated (HCN) channel family, of which HCN4 is predominant in mammalian heart. Both loss-of-function and gain-of-function mutations of the HCN4 gene are associated with sinus node dysfunction in humans; however, their functional impact is not fully understood yet. Here, we sought to characterize a HCN4 V759I variant detected in a patient with a family history of sick sinus syndrome. The genomic analysis yielded a mono-allelic HCN4 V759I variant in a 49-year-old woman presenting with a family history of sick sinus syndrome. This HCN4 variant was previously classified as putatively pathogenic because genetically linked to sudden infant death syndrome and malignant epilepsy. However, detailed electrophysiological and cell biological characterization of HCN4 V759I in Xenopus laevis oocytes and embryonic rat cardiomyocytes, respectively, did not reveal any obvious abnormality. Voltage dependence and kinetics of mutant channel activation, modulation of cAMP-gating by the neuronal HCN channel auxiliary subunit PEX5R, and cell surface expression were indistinguishable from wild-type HCN4. In good agreement, the clinically likewise affected mother of the patient does not exhibit the reported HCN4 variance. HCN4 V759I resembles an innocuous genetic HCN channel variant, which is not sufficient to disturb cardiac pacemaking. Once more, our work emphasizes the importance of careful functional interpretation of genetic findings not only in the context of hereditary cardiac arrhythmias.

scholarly journals The effect of temperature on spontaneous action potential discharge of the isolated sinus venosus from winter and summer plaice (Pleuronectes platessa)

1995 ◽  
Vol 198 (1) ◽  
pp. 137-140 ◽  
Author(s):  
A A Harper ◽  
I P Newton ◽  
P W Watt
Keyword(s):  
Action Potential ◽  
Discharge Rate ◽  
Cardiac Pacemaker ◽  
Intrinsic Rate ◽  
Effect Of Temperature ◽  
Pacemaker Activity ◽  
Duration Of Action ◽  
Diastolic Depolarization ◽  
Significant Difference

The spontaneous cardiac pacemaker activity and conformation were recorded in vitro, using intracellular recording methods, from heart tissue of summer- and winter-caught plaice. The effects of changing temperature on the pacemaker rate, duration of action potential and diastolic depolarization were investigated by altering the temperature of the superfusing medium. The resting intrinsic rate of discharge was significantly greater in pacemaker cells from winter plaice (P=0.05), but there was no significant difference between winter and summer fish in the apparent Arrhenius activation energies for this process. However, there was a significant difference in the estimated intercept, indicating a thermal shift in the processes underlying the spontaneous pacemaker rhythm. There was no significant difference in the diastolic depolarization duration recorded from winter and summer fish over the temperature range 4­22 °C. The major effect of previous environmental temperature was on the duration of the action potential (P<0.02), indicating that the observed changes in pacemaker discharge rate were not influenced by the processes that determine the duration of the pacemaker diastolic depolarisation but were modulated by the channel events that give rise to the action potential.

Cellular and subcellular mechanisms of cardiac pacemaker oscillations

1979 ◽  
Vol 81 (1) ◽  
pp. 205-215
Author(s):  
R. W. Tsien ◽  
R. S. Kass ◽  
R. Weingart
Keyword(s):  
Membrane Potential ◽  
Voltage Clamp ◽  
Surface Membrane ◽  
Cardiac Pacemaker ◽  
Oscillatory Activity ◽  
Purkinje Fibre ◽  
Pacemaker Activity ◽  
Heart Cells ◽  
Control Loop ◽  
Internal Oscillation

Rhythmic oscillations in the membrane potential of heart cells are important in normal cardiac pacemaker activity as well as cardiac arrhythmias. Two fundamentally different mechanisms of oscillatory activity can be distinguished at the cellular and subcellular level. The first mechanism, referred to as a surface membrane oscillator, can be represented by a control loop in which membrane potential changes evoke delayed conductance changes and vice versa. Since the surface membrane potential is a key variable within the control loop, the oscillation can be interrupted at any time by holding the membrane potential constant with a voltage clamp. This mode of oscillation seems to describe spontaneous pacemaker activity in the primary cardiac pacemaker (sinoatrial node) as well as other regions (Purkinje fibre, atrial or ventricular muscle). In all tissues studied so far, the pacemaker depolarization is dominated by the slow shutting-off of an outward current, largely carried by potassium ions. The second mechanism can be called an internal oscillator since it depends upon a subcellular rhythm generator which is largely independent from the surface membrane. Under voltage clamp, the existence of the internal oscillation is revealed by the presence of oscillations in membrane conductance or contractile force which occur even though the membrane potential is held fixed. The two oscillatory mechanisms are not mutually exclusive; the subcellular mechanism can be preferentially enhanced in any given cardiac cell by conditions which elevate intracellular calcium. Such conditions include digitalis intoxication, high Cao, low Nao, low or high Ko, cooling, or rapid stimulation. Several lines of evidence suggest that the subcellular mechanism involves oscillatory variations in myoplasmic calcium, probably due to cycles of Ca uptake and release by the sarcoplasmic reticulum. The detailed nature of the Cai oscillator and its interaction with the surface membrane await further investigation.

Effects of current flow on pacemaker activity of the isolated kitten sinoatrial node

1980 ◽  
Vol 238 (3) ◽  
pp. H307-H316 ◽  
Author(s):  
J. Jalife ◽  
A. J. Hamilton ◽  
V. R. Lamanna ◽  
G. K. Moe
Keyword(s):  
Response Curve ◽  
Current Flow ◽  
Sinoatrial Node ◽  
Phase Response Curve ◽  
Vagal Stimulation ◽  
Cardiac Pacemaker ◽  
Phase Response ◽  
Pacemaker Activity ◽  
Current Pulses ◽  
Sucrose Gap

The dynamic behavior of the cardiac pacemaker in response to single or to periodically repeated perturbations was studied using kitten sinoatrial (SA) nodal strips mounted in a sucrose gap. Sustained stepwise applications of current across the gap produce lasting variations in pacemaker cycle length that depend on current magnitude and polarity, but not on the phase of the pacemaker period at the time of the input. Brief current pulses, whether hyperpolarizing or depolarizing, may abbreviate or prolong the immediately affected cycle depending on their timing. These changes result in phase shifts of the subsequent discharges, but they do not alter the pacemaker period permanently. The phasic effects of brief current pulses can be described by a phase response curve (PRC), which is a plot of the phase shift as a function of the position of the stimulus in the pacemaker cycle. PRCs were constructed for inputs of different polarity and several strengths and durations. The behavior of the sinus nodal pacemaker when interacting with period perturbing inputs, such as vagal stimulation or electrotonic depolarization, can be predicted on the basis of the phase response curve.

scholarly journals PP2 Prevents Isoproterenol Stimulation of Cardiac Pacemaker Activity

2015 ◽  
Vol 65 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Jianying Huang ◽  
Yen-Chang Lin ◽  
Stan Hileman ◽  
Karen H. Martin ◽  
Robert Hull ◽  
...  
Keyword(s):  
Cardiac Pacemaker ◽  
Pacemaker Activity ◽  
Stimulation Of

scholarly journals Electrophysiology of an Insect Heart

1963 ◽  
Vol 46 (4) ◽  
pp. 803-821 ◽  
Author(s):  
Frances V. McCann
Keyword(s):  
Action Potentials ◽  
Single Cells ◽  
Cardiac Pacemaker ◽  
Concentration Gradients ◽  
Virtual Absence ◽  
A Value ◽  
Structural Differences ◽  
Intracellular Microelectrodes ◽  
Extracellular Sodium

Bioelectric activity in single cells of the moth myocardium has been measured in situ with intracellular microelectrodes with particular reference to the bizarre ionic medium which bathes the tissues. Resting potentials averaged 47 mv, inside negative with respect to outside, despite a value of 11 mv calculated on the basis of transmembrane potassium concentration gradients. Action potentials overshoot as much as 12 mv in the virtual absence of extracellular sodium. Two "types" of action potentials have been recorded; one that resembles vertebrate atrial action potentials is found in the cephalic region of the tubular heart, and the other, similar in contour to vertebrate ventricular action potentials, is found in the areas posterior to the first abdominal segment. Histological sections indicate no structural differences between the two areas. Typical cardiac pacemaker type potentials occur but are not topographically localized. The effects of the omission from the perfusion fluid of the four major cationic constituents, Na+, K+, Ca++ and Mg++, on resting and action potentials may be summarized as: no effect, hyperpolarization, prolonged repolarization, and depolarization, respectively.

scholarly journals Basal Phospholipase C (PLC) Activation is Obligatory for Cardiac Pacemaker Activity

2011 ◽  
Vol 100 (3) ◽  
pp. 517a ◽  
Author(s):  
Tatiana M. Vinogradova ◽  
Edward G. Lakatta
Keyword(s):  
Phospholipase C ◽  
Cardiac Pacemaker ◽  
Pacemaker Activity
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