Node Myocytes Research Articles

The effects of manganese and barium on the cardiac pacemaker current, i f , in rabbit sino-atrial node myocytes

The isolation of ionic fluxes contributing to electric currents through cell membranes often requires block of other undesired components which can be achieved, among others, by divalent cations. Mn2+ and Ba2+ are often used, for example, to block Ca and K currents. Here we have investigated the effects of these two cations on the properties of the hyperpolarization-activated pacemaker current if, in rabbit sino-atrial node myocytes, as obtained by voltage clamp analysis. We find that 2 mM Mn2+ shifts the if activation curve by 3.2 +/- 0.3 mV towards more positive values. However, when 1 mM Ba2+ is also added, the positive shift is more than halved (1.3 +/- 0.2 mV). We find, too, that in the absence of blocking cations the ACh-induced if inhibition is slightly higher than in their presence. These results indicate that the alteration of if kinetic properties by Ba2+ plus Mn(2+)-containing solutions is minimal.

The contribution of the ‘pacemaker’ current (if) to generation of spontaneous activity in rabbit sino‐atrial node myocytes.

1. The contribution to the diastolic depolarization of the hyperpolarization-activated current, if, relative to other components was investigated in isolated rabbit sino-atrial (SA) node myocytes. 2. During the diastolic phase the membrane potential depolarized by 0.1096 +/- 0.014 V/s, which requires only about 3 pA of inward current in a cell with an average capacity of 30 pF. The problem of which ionic component is responsible for initiating the diastolic depolarization was investigated by analysing the composition and the properties of the net inward current in the diastolic range of voltages. 3. The measured instantaneous 'background' current activated during voltage clamp steps from a holding potential of -35 mV was outward positive to approximately -61 mV, and had a region of negative slope conductance from -45 to -35 mV. 4. The instantaneous component lost its rectifying behaviour in the presence of Ni2+ (100 microM) and nitrendipine (10 microM). These blockers of Ca(2+)-dependent currents modified the instantaneous I-V relation at voltages positive to -45 to -50 mV, thus implying that Ca2+ currents become important at less negative potentials than -50 mV, towards the very end of diastolic depolarization. 5. Possible errors introduced by voltage clamp analysis with the whole-cell method on the instantaneous current and on if measurement were evaluated. Leakage through the seal resistance caused the instantaneous I-V relation to be displaced in the inward direction at negative voltages. Correction for the seal leakage moved the reversal potential for the instantaneous current toward the negative direction from -61 to approximately -66 mV. Thus, no depolarization can be driven by the background current beyond -66 mV. 6. During voltage clamp analysis, lack of series-resistance compensation led to lack of intracellular voltage control, as was apparent using a second pipette on the same cell. This slowed activation of if and led to a 1.5- to 2-fold reduction of if size in the range -55 to -115 mV. Thus, uncorrected measurements of the instantaneous component and of if may concur to underestimate the role of if in pacemaking. 7. These results lead to the conclusion that in the SA node cells analysed, pacemaker activity is generated with the essential contribution of the hyperpolarization-activated current, if. Numerical computation of SA node cell activity using an extension of the DiFrancesco-Noble model shows that the if-activation hypothesis can account for the presence of spontaneous action potentials and their sensitivity to if changes.

Block of the cardiac pacemaker current (If) in the rabbit sino-atrial node and in canine Purkinje fibres by 9-amino-1,2,3,4-tetrahydroacridine

We have investigated the action of 9-amino-1, 2, 3, 4-tetrahydroacridine (THA) on the pacemaker current If in rabbit sino-atrial node myocytes and in canine Purkinje fibers. THA at concentrations in the range 3-300 microM blocked If in a voltage-independent manner, as revealed by measurements on the fully activated I/V relation for If. The dose/response relationship of the If maximal slope conductance (Gf) can be fitted by assuming a cooperative binding reaction where two THA molecules are required to block one If channel. Half-maximal block occurred at 18.2 microM in the sino-atrial node and 36.6 microM in Purkinje fibers. THA also affected the If kinetic properties. This was examined in the sino-atrial node where the current activation curve was shifted in the negative direction on the voltage axis (- 21 mV at 30 microM THA). The delayed rectifier current, IK, was also reduced by THA in sino-atrial node myocytes: at - 40 mV the IK fully activated value was decreased to 37% of its control value by 30 microM THA, with only a minor modification of the position of the activation curve at the same potential. Thus, although THA blocks If at a lower concentration than other known If-channel blockers [DiFrancesco (1982) J Physiol (Lond) 329:485-507], its action on the pacemaker current is not specific.

Wenckebach periodicity in single atrioventricular nodal cells from the rabbit heart.

Previous studies have suggested that Wenckebach periodicity in cardiac tissues may occur because of discontinuous propagation across junctional areas in which there is high intercellular resistivity or different cell types. Under these conditions, the impulse may stop altogether at a given junction, or may renew its propagation but only after a step delay imposed by the diastolic time-dependent recovery in the excitability of cells distal to that junction. Accordingly, Wenckebach periodicity in the atrioventricular node may be explained in terms of electrotonically mediated delay in the activation of the nodal cells. To test this hypothesis, we have studied recovery of excitability, and susceptibility to rate-dependent activation failure in single myocytes isolated from the adult rabbit atrioventricular node. Recordings were obtained by using the patch technique in the whole-cell, current clamp configuration. Repetitive stimulation of single atrioventricular nodal myocytes with depolarizing current pulses of critical amplitude yielded frequency-dependent stimulus response patterns that ranged from 1:1, through various Wenckebachlike periodicities (e.g., 5:4 and 4:3) to 2:1 and 3:1. Both typical and atypical Wenckebach structures were demonstrated, as well as "complex" patterns (e.g., reverse Wenckebach or alternating Wenckebach) previously ascribed to multiple levels of block. The diastolic recovery of excitability curve, determined by application of repetitive stimuli at cycle lengths that were longer than the action potential duration, showed a monotonic function with a refractory period outlasting the action potential duration (i.e., postrepolarization refractoriness). Abbreviation of the stimulation cycle length to values below those of the action potential duration revealed the existence of a period of supernormal excitability during the repolarizing phase of the action potential. In either case, the stimulus response patterns obtained were a direct consequence of the shape of the recovery of excitability curve. The monotonic portion of the recovery curve was fitted to an empirical equation that when iterated reproduced the stimulus response patterns observed in the atrioventricular nodal cell. Our data demonstrate that recovery of excitability after an action potential is indeed a function of the diastolic interval, and that this slow process sets the conditions for the development of Wenckebach periodicity in the atrioventricular node.

An immunocytochemical study of the sinuatrial node and atrioventricular conducting system of the rat for atrial natriuretic peptide distribution

Immunocytochemical studies of the adult rat heart show that specific heart granules and atrial natriuretic peptide immunoreactivity are absent from the majority of the myocytes of the specialized nodes, atrioventricular bundle and bundle branches. Immunoreactive granules are present in a small proportion of the transitional sinuatrial and atrioventricular nodal myocytes but, in these regions, they are smaller than their counterparts in the general atrial myocytes. A rarer type of cell profile, identical to general atrial myocytes but lacking immunoreactive granules, is also present at the periphery of the sinuatrial node. A very small proportion of myocytes in the ventricular myocardium, generally in the subendocardial layers subjacent to the terminal ramifications of the bundle branches, contain a few immunoreactive granules.

Muscarinic control of the hyperpolarization‐activated current (if) in rabbit sino‐atrial node myocytes.

1. The mechanism by which acetylcholine (ACh), by stimulation of muscarinic receptors, acts to inhibit activation of the hyperpolarization-activated 'pacemaker' current, if was investigated in isolated rabbit sino-atrial (SA) node myocytes. 2. Intracellular loading with GTP gamma S, a non-hydrolysable analogue of GTP, did not impair the ACh action on if, but made it irreversible. On the other hand, the ACh action on if disappeared after a few minutes of cell loading with GDP beta S, a GDP analogue known to bind to G-proteins and prevent their receptor-stimulated action. Furthermore, incubation of cells in a solution containing pertussis toxin (PTX) led to abolition of the if response to ACh. These results indicate that the inhibitory effect of ACh on if is mediated by G-proteins activated by muscarinic receptors. 3. Intracellular loading with phosphodiesterase (PDE) increased the rate of if current run-down, but did not abolish the inhibitory action of ACh on if. 4. Extracellular perfusion with isobutylmethylxanthine (IBMX), a PDE inhibitor, increased if activation by shifting the current activation range to more positive voltages, as inferred by a three-pulse protocol analysis; in the presence of IBMX, the inhibition of if by ACh was not abolished. 5. The ACh-induced if depression persisted also in cells loaded with cyclic GMP. In these cells, as in those loaded with PDE, the if run-down was fast. 6. Oxotremorine, a muscarinic agonist coupled to adenylate cyclase but not to phosphoinositide turnover in cardiac cells, simulated ACh in its inhibitory action on if. The above results rule against the ACh action being mediated by PDE or by phosphoinositide turnover. 7. To investigate the possible involvement of cyclic AMP as a second messenger in the ACh action on if, we loaded cells with cyclic AMP and IBMX; under these conditions the action of ACh disappeared within a few minutes of whole-cell recording. 8. In cells where the slow inward Ca2+ current (isi) was measured together with if, ACh was seen to depress both currents. 9. In cells superfused with forskolin, the if amplitude on stepping to the half-activation voltage range was enhanced as a consequence of a depolarizing shift of the activation curve; ACh was not effective on if following stimulation by forskolin, but strongly depressed in the same cell the if current stimulated to a similar degree by isoprenaline.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of the hyperpolarization-activated current (if) induced by acetylcholine in rabbit sino-atrial node myocytes.

1. The action of acetylcholine (ACh) on the hyperpolarization-activated ('pacemaker') current if was studied in single myocytes from the sino-atrial (SA) node region of the rabbit heart, where low doses of ACh slow spontaneous activity by prolonging the diastolic depolarization phase. 2. Besides activating an outward component at voltages positive to the K+ equilibrium potential (iK,ACh), ACh depressed the current if activated on hyperpolarization at concentrations in the range 0.03-1 microM. 3. The ACh-dependent if depression was dissected from modifications of iK,ACh by blocking iK,ACh with barium and was studied under conditions that minimized the interference of other current changes caused by ACh. 4. The study of if modification by ACh with three-pulse protocols and the measurement of fully activated I-V relations of if with and without ACh revealed that ACh acted on if by shifting the current activation range to more negative voltages, with no obvious alteration of the fully activated current amplitude. 5. The action of ACh on if was opposite to that caused by catecholamines. The presence of isoprenaline (IP) did not prevent ACh inhibition of if, nor did the presence of ACh prevent the if stimulation caused by IP. The effects of IP and ACh on if were additive. 6. The ACh-induced inhibition of if was reversed by addition of atropine and could be mimicked by muscarine, indicating that muscarinic receptors mediate it. The implications of these findings on the regulation of pacemaker activity by ACh is discussed.

The structure and innervation of the sinu-atrial node of the mole heart.

The sinu-atrial node in the heart of the mole, Mogera wogera, contains myocytes which are devoid of atrial specific granules and which may be classified into two types: electron-lucent (majority) and dark (minority). Numerous unmyelinated axon terminals, containing synaptic vesicles, face the nodal myocyte surface with interspaces of less than 300 nm. There are about 6 terminals per myocyte profile and about 10 per profile at nuclear levels. Of a total of 2717 of these terminals 85.2% are 50-200 nm from the nodal myocytes, and 9.6% form closer neuromuscular junctions, with less than 50 nm interspace and some membrane specialization. Such specilizations are almost exclusively found in relation to the dark, minority-type of nodal myocyte. Myelinated nerve fibers are also numerous within the mole SA node, and may terminate almost directly on a nodal myocyte. A few nerve fibers contain many mitochondria and may represent afferent endings. Nodal capillaries are smaller and fewer than capillaries in the juxtanodal myocardium, probably indicating a lesser blood supply to the SA node than to the ordinary myocardium.

Plasma electrolytes, pH, and ECG during and after exhaustive exercise.

ArticlePlasma electrolytes, pH, and ECG during and after exhaustive exercise.N Coester, J C Elliott, and U C LuftN Coester, J C Elliott, and U C LuftPublished Online:01 May 1973https://doi.org/10.1152/jappl.1973.34.5.677MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByAtrial and ventricular tachyarrhythmias in military personnel5 August 2015 | Journal of the Royal Army Medical Corps, Vol. 161, No. 3Interpretation of ECG and Subjective Responses (Chest Pain)Vagal control of heart rate is modulated by extracellular potassiumJournal of the Autonomic Nervous System, Vol. 77, No. 2-3Hyperkalemia Enhances the Effect of Adenosine on I K,ADO in Rabbit Isolated AV Nodal Myocytes and on AV Nodal Conduction in Guinea Pig Isolated HeartCirculation, Vol. 99, No. 2Haematological and biochemical changes in horses competing in a 3 Star horse trial and 3-day-event10 June 2010 | Equine Veterinary Journal, Vol. 27, No. S20Exercise-Induced Renal and Electrolyte Changes18 December 2017 | The Physician and Sportsmedicine, Vol. 23, No. 8Disorders of Potassium BalancePediatric Annals, Vol. 24, No. 1Influence of Postexercise Glucose Ingestion upon Serum Potassium Levels and ECG FunctionInternational Journal of Sport Nutrition, Vol. 4, No. 1Methacholine Airway Responsiveness and 24-Hour Urine Excretion of Sodium and Potassium: The Normative Aging StudyAmerican Review of Respiratory Disease, Vol. 144, No. 3_pt_1Effect of show jumping on heart rate, blood lactate and other plasma biochemical values10 June 2010 | Equine Veterinary Journal, Vol. 22, No. S9Effects of exercise testing, training and beta blockade on serum potassium in normal subjectsThe American Journal of Cardiology, Vol. 65, No. 18Changes in arterial plasma potassium and ventilation during exercise in manRespiration Physiology, Vol. 78, No. 3Exercise stress-induced changes in systemic arterial potassium in angina pectorisThe American Journal of Cardiology, Vol. 63, No. 20Exercise-related changes in serum catecholamines and potassium: Effect of sustained exercise above and below lactate thresholdAmerican Heart Journal, Vol. 117, No. 5Effets de l'exposition au froid sur les variations plasmatiques du lactate et des ions induites par un exercice musculaire aérobie intenseScience & Sports, Vol. 2, No. 1Hypotension and sinus arrest with exercise-induced hyperkalemia and combined verapamil/propranolol therapyThe American Journal of Medicine, Vol. 80, No. 6Catecholamine Modulation of Rapid Potassium Shifts during ExerciseNew England Journal of Medicine, Vol. 312, No. 13Physiologic changes during a marathon, with special reference to magnesium.Journal of the American College of Nutrition, Vol. 4, No. 2Acute effects on chromium, copper, zinc, and selected clinical variables in urine and serum of male runnersBiological Trace Element Research, Vol. 6, No. 4Changes in plasma biochemistry in horses competing in a 160 km endurance rideAustralian Veterinary Journal, Vol. 60, No. 4HYPOTHERMIA, HYPERKALAEMIA, AND MARATHON RUNNINGThe Lancet, Vol. 320, No. 8311IS METASTATIC BREAST CARCINOMA IN THE PITUITARY A CONCEALED MANIFESTATION?The Lancet, Vol. 320, No. 8311Potassium Disposition and Neuroendocrine Effects of Propranolol, Methyldopa and Clonidine During Dynamic Exercise3 July 2009 | Clinical and Experimental Hypertension. Part A: Theory and Practice, Vol. 4, No. 9-10Variations in normal electrocardiographic response to treadmill testingThe American Journal of Cardiology, Vol. 47, No. 5ELECTROCARDIOGRAPHY AND HAEMATOLOGY OF HORSES COMPETING IN A THREE-DAY EVENTAustralian Veterinary Journal, Vol. 56, No. 7Plasma biochemistry in the horse during 3-day event competitionEquine Veterinary Journal, Vol. 12, No. 3Quantification of human plasma inorganic pyrophosphateArthritis & Rheumatism, Vol. 22, No. 8ELECTROCARDIOGRAPHY, HEART SCORE AND HAEMATOLOGY OF HORSES COMPETING IN AN ENDURANCE RIDEAustralian Veterinary Journal, Vol. 55, No. 6Dynamic electrocardiography II a crucial test of the electromechanical QRS wave theoryMedical Hypotheses, Vol. 5, No. 5 More from this issue > Volume 34Issue 5May 1973Pages 677-82 https://doi.org/10.1152/jappl.1973.34.5.677PubMed4703745History Published online 1 May 1973 Published in print 1 May 1973 Metrics

THE INITIATION OF IMPULSES IN CARDIAC MUSCLE

ArticleTHE INITIATION OF IMPULSES IN CARDIAC MUSCLEEmil BozlerEmil BozlerFrom the Department of Physiology, the Ohio State University, ColumbusPublished Online:01 Jan 1943https://doi.org/10.1152/ajplegacy.1943.138.2.273MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByFocus, reentry, or “focal” reentry?Michiel J. Janse1 June 2007 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 292, No. 6Contribution of L-type Ca2+current to electrical activity in sinoatrial nodal myocytes of rabbitsE. Etienne Verheijck, Antoni C. G. van Ginneken, Ronald Wilders, and Lennart N. Bouman1 March 1999 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 276, No. 3The effects of tension on acetylstrophanthidin-induced transient depolarizations and aftercontractions in canine myocardial and Purkinje tissues.Circulation Research, Vol. 38, No. 3 More from this issue > Volume 138Issue 2January 1943Pages 273-282 Copyright & PermissionsCopyright © 1943 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1943.138.2.273History Received 28 August 1942 Published online 1 January 1943 Published in print 1 January 1943 Metrics