Role of voltage oscillations in the automaticity of sheep cardiac Purkinje fibers

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The mechanisms by which low [K⁺]_o induces spontaneous activity was studied in sheep Purkinje fibers. Purkinje strands were superfused in vitro and membrane potentials were recorded by means of a microelectrode technique. The results show that low [K⁺]_o increases the slope and amplitude of early diastolic depolarization, sharpens the transition between early and late diastolic depolarizations, induces an after-potential and large pre-potentials through a negative shift of an oscillatory zone. Pre-potentials occur progressively sooner during diastole and merge with the after-potential to induce uninterrupted spontaneous discharge. During recovery, when the rate slows, after- and pre-potentials separate once more, the slower discharge decreasing the after-potentials but not the pre-potentials. Low [K⁺]_o has little effect on the plateau, but markedly slows phase 3 repolarization and may altogether prevent it. At depolarized levels, voltage oscillations, slow responses, sinusoidal fluctuations or quiescence may be present depending on voltage. During the recovery, a train of either sub-threshold oscillations or spontaneous action potentials appear towards the end of phase 3 repolarization. The cessation of the action potentials unmasks large sub-threshold oscillations, that occur in the oscillatory zone. Drive, high [Ca²⁺]_o and norepinephrine increase slope and amplitude of early diastolic depolarization as low [K⁺]_o does. In low [K⁺]_o, Cs⁺ prevents spontaneous discharge at polarized levels, but not the decrease in resting potential nor the onset of slow responses at depolarized levels. Cs⁺ blocks the train of oscillations and of action potentials occurring during recovery. We conclude that low [K⁺]_o steepens early diastolic depolarization and increases its amplitude through an after-potential that results from an increased Ca²⁺ load; allows the attainment of the threshold through Cs⁺-sensitive voltage oscillations which develop when the oscillatory zone is entered either by diastolic depolarization or by phase 3 repolarization; and causes voltage oscillations also at depolarized levels, but through a Cs⁺-insensitive different mechanism.

Section: Methodsmentioning

confidence: 99%

Section: Prevention Of the Effect Of Low [K + ] O By Cromakalimmentioning

confidence: 99%

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Oscillatory Zones and Their Role in Normal and Abnormal Sheep Purkinje Fiber Automaticity

Berg

Vassalle

2000

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“…TTX would act not by preventing the Na + -Ca 2+ exchange, but rather by decreasing Na + entry, [Na + ] i and therefore Ca 2+ overload through a greater Na + gradient. An additional factor might be the suppression of the depolarizing phase of the diastolic oscillations (ThV os [94]) that even in the absence of digitalis are needed for the attainment of the threshold [77,89].…”

Section: Role Of Na + In Electrical Toxicitymentioning

confidence: 99%

Calcium Overload and Cardiac Function

Vassalle

Chen

2004

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The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca²⁺ may increase in different structures [e.g. sarcoplasmic reticulum (SR), cytoplasm and mitochondria] to an excessive level which induces electrical and mechanical abnormalities in cardiac tissues. The electrical manifestations of Ca²⁺ overload include arrhythmias caused by oscillatory (V_os) and non-oscillatory (V_ex) potentials. The mechanical manifestations include a decrease in force of contraction, contracture and aftercontractions. The underlying mechanisms involve a role of Na⁺ in electrical abnormalities as a charge carrier in the Na⁺-Ca²⁺ exchange and a role of Ca²⁺ in mechanical toxicity. Ca²⁺ overload may be induced by an increase in [Na⁺]_i through the inhibition of the Na⁺-K⁺ pump (e.g. toxic concentrations of digitalis) or by an increase in Ca²⁺ load (e.g. catecholamines). The Ca²⁺ overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca²⁺ overload than myocardial fibers, possibly because of their greater Na⁺ load. If the SR is predominantly Ca²⁺ overloaded, V_os and fast discharge are induced through an oscillatory release of Ca²⁺ in diastole from the SR; if the cytoplasm is Ca²⁺ overloaded, the non-oscillatory V_ex tail is induced at negative potentials. The decrease in contractile force by Ca²⁺ overload appears to be associated with a decrease in high energy phosphates, since it is enhanced by metabolic inhibitors and reduced by metabolic substrates. The ionic currents I_os and I_ex underlie V_os and V_ex, respectively, both being due to an electrogenic extrusion of Ca²⁺ through the Na⁺-Ca²⁺ exchange. I_os is an oscillatory current due to an oscillatory release of Ca²⁺ in early diastole from the Ca²⁺-overloaded SR, and I_ex is a non-oscillatory current due to the extrusion of Ca²⁺ from the Ca²⁺-overloaded cytoplasm. I_os and I_ex can be present singly or simultaneously. An increase in [Ca²⁺]_i appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, [Ca²⁺]_i may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca²⁺-overloaded cardiac cells by decreasing the inhibition of the Na⁺-K⁺ pump by Ca²⁺, thereby leading to a reduction in Ca²⁺ overload and to an increase in force of contraction.

“…Under certain conditions, two types of oscillatory po tentials can be simultaneously present both in Purkinje fibers [4,22] and in the sinoatrial node (SAN) [12], One is an q/terpotential which is superimposed on and steepens the initial diastolic depolarization, DD (Vos). The other is a /vepotential which occurs during the late DD near the threshold for the upstroke (ThV0S).…”

Section: Osmentioning

confidence: 99%

Overdrive Excitation in the Guinea Pig Sinoatrial Node Superfused in High [K+](0)

Choy¹,

Kim²,

Vassalle³

1997

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The aim of the present experiments was to study the characteristics and mechanisms of the rhythm induced by overdrive (‘overdrive excitation’, ODE) in the sinoatrial node (SAN) superfused in high [K^+](0) (8-14 mM). It was found that; (1) overdrive may induce excitation in quiescent SAN and during a slow drive; (2) in spontaneously active SAN, overdrive may accelerate the spontaneous discharge; (3) immediately after the end of overdrive, a pause generally precedes the onset of the induced rhythm; (4) during the pause, an oscillatory potential (V(os)) may be superimposed on the early diastolic depolarization (DD); (5) during the subsequent late DD, a different kind of oscillatory potential appears near the threshold for the upstroke (ThV(os)) which is responsible for the initiation of spontaneous activity; (6) once started, the induced rhythm is fastest soon after overdrive; (7) faster drives induce longer and faster spontaneous rhythms; (8) the induced action potentials are slow responses followed by DD with a superimposed Vos, but ThV(os) is responsible for ODE; (9) the induced rhythm subsides when ThV(os) miss the threshold and gradually decay; (10) low [Ca^2+](0) abolishes ODE; (11) in quiescent SAN, high [Ca^2+](0) induces spontaneous discharge through ThV(os) and increases its rate by enhancing V(os) and shifting the threshold to more negative values, and (12) tetrodotoxin abolishes ODE as well as the spontaneous discharge induced by high [Ca^2+](0). In conclusion, in K^+-depolarized SAN, ODE may be present in the apparent absence of calcium overload, is Ca^2+- and Na^+-dependent and is mediated by ThV(os) and not by V(os).