Maximum Rate Of Depolarization Research Articles

Electrophysiologic antagonism and synergism of potassium and antiarrhythmic agents

Interactions of potassium and antiarrhythmic agents on ventricular myocardial electrophysiology were studied in 25 isolated, perfused rabbit hearts by utilizing an intracellular microelectrode technic. Perfusion of quinidine (0.01 mg./ml.) in a normal concentration of potassium (5.6 mEq./L.) caused a significant decrease in the maximal rate of depolarization (−69.1%), heart rate (−40.4%) and the action potential duration per unit of time (−13.8%). Reduction in the height of action and resting potentials was insignificant. Lowering potassium to 0.8 mEq./L., in the presence of the same concentration of quinidine, significantly increased the maximal rate of depolarization (+82.5%), the height of action potential (+8.5%) and resting potential (+9.9%). The action potential duration per unit of time also showed a significant increase (+15.2%) to control value, although the heart rate was further decreased. Initial perfusion of a low potassium solution caused a significant increase in the height of action potential (+3.3%) and resting potential (+7.0%) as well as a significant decrease in the action potential duration per unit of time (−19.2%). The maximal rate of depolarization and the heart rate showed no significant changes. Addition of quinidine to this low potassium perfusate did not produce any appreciable changes in the maximal rate of depolarization, or in the height of action and resting potentials. The action potential duration per unit of time again returned to its control level. Hence, the electrophysiologic action of quinidine was nullified by a low potassium concentration in both groups of experiments. Quite a similar antagonism was demonstrated between low potassium concentration and other antiarrhythmic agents (antazoline and SU-11636), while high potassium concentration (12 mEq./L.) enhanced the depressive effects of these three drugs. The electrophysiologic mechanism of antiarrhythmic agents was discussed, and the clinical importance of controlling serum potassium concentration during the administration of these agents was suggested.

Intracellular ionic injection in rabbit ventricular fibres.

SUMMARYBy means of double‐barrelled microelectrodes filled with appropriate salt solutions we have observed the effects of injecting, iontophoretically, sodium, potassium and chloride ions into muscle fibres of the rabbit right ventricle.Injection of sodium ions produced a reversible decline in maximum rate of depolarisation and amplitude of the action potential with no change in shape or voltage‐time course of the action potential.Injection at equivalent rates of equivalent amounts of potassium or chloride ions had no effect.The changes observed after sodium injection are in agreement with the prediction of the mathematical model of the cardiac action potential described by George and Johnson (1962).

Effects of calcium deficiency and excess on transmembrane potentials in frog heart.

The effects of severe calcium deficiency and calcium excess on transmembrane potentials in isolated frog ventricular strips have been investigated. Resting potential rose about 5 mv above normal during perfusion with three times normal calcium and fell about 4 mv below normal during exposure to calcium-free Clark's solution. Mean overshoot rose about 3 mv during calcium lack, but was unaffected by excess calcium. Maximum depolarization rate increased about 20% during calcium deprivation and fell a similar amount during high calcium perfusion. However, the membrane potential at the moment of maximum depolarization rate was unchanged from normal by either experimental solution. High calcium augmented the "spike" and "plateau" during repolarization, while calcium deficiency abolished the spike, producing "hump-backed" action potentials with prolonged membrane reversal. These results are discussed, especially in relation to possible permeability changes during upstroke of the action potential.

Effects of calcium deficiency on cell membrane potentials of isolated frog hearts.

Membrane potentials were recorded in isolated frog hearts. Observations were made on the effects of calcium deficiency upon resting potential, action potential, overshoot, maximum depolarization rate and action potential contour. Calcium deficiency caused a significant fall in all observed potentials. Maximum depolarization rate was increased. Early repolarization rate was markedly decreased. Chelation of calcium caused changes indistinguishable from those caused by omission of the ion from the perfusate. These results are discussed in relation to current concepts.

THE ELECTRICAL PROPERTIES OF THE SMOOTH MUSCLE CELL MEMBRANE

In myometrium from pregnant cat, repetitive action potentials have been recorded during contraction. Using intracellular electrodes the depolarizations averaged 35 mv. Maximum rate of depolarization was 1–2 v/sec and the action potential duration varied from 250 milliseconds to much longer periods. Membrane reversal of up to 10 mv sometimes occurred. Total resistance decreased during depolarization and recovered during repolarization. Typical biphasic potentials were also recorded with extracellular electrodes. Their amplitude (peak to peak) varied from 0.3 to several millivolts and their duration (peak to peak) from 10–40 milliseconds. Reduction of external sodium concentration to as little as one-ninth normal (choline chloride or sucrose replacement) did not reduce the amplitudes of the resting or action potentials measured intracellularly or extracellularly, but decreased the action potential frequency. Membrane reversal still occurred with intracellular electrodes and the maximum rate of depolarization was unchanged. The rate of repolarization was increased so that the total duration of the action potential was 150 to 200 milliseconds. With extracellular electrodes, the peak to peak amplitudes were increased and the durations were unchanged. Further reduction of external sodium concentration to less than 15–20 meq/liter caused a contraction without further change in action potential configuration. Gradual relaxation and slowing of the repetition rate of action potentials occurred and resulted eventually in complete mechanical and electrical inactivity.Rabbit taenia coli were also studied and their electrical properties contrasted to those of cat myometrium. The conclusions were reached that: (1) the available evidence opposes the hypotheses that an inward sodium current accounts for depolarization in smooth muscle and (2) smooth muscles differed in their electrical properties and mechanisms of ion distribution not only from striate muscles but also from one another.

The stimulatory action of acetylcholine on isolated rabbit atria.

Quinidine (2.5 to 5x10(-6) g./ml.) decreased the maximum rate of depolarization of the action potentials (AP) of both isolated rabbit atrial and ventricular fibres recorded with an intracellular microelectrode and finally abolished electrical excitability and spontaneous rhythmicity. Acetylcholine (ACh) 10(-6) restored these properties in the atrium (but not ventricle) without changing the membrane resting potential (MRP). Adrenaline 10(-6) to 10(-4) at the same time was without effect. The maximum rate of depolarization of an AP in response to an extra shock interposed between the 8th and 9th driving stimuli was increased by ACh 10(-6) in atria which had received quinidine to a greater extent than that of the normal AP. It is suggested that ACh restarted atria arrested by quinidine by an action on the sodium "carrying system" (excitatory mechanism) and this was not the result of an increase in MRP. An hypothesis is put forward to explain the stimulatory and inhibitory effects of ACh on rabbit atria.

THE ELECTRICAL PROPERTIES OF THE SMOOTH MUSCLE CELL MEMBRANE

In myometrium from pregnant cat, repetitive action potentials have been recorded during contraction. Using intracellular electrodes the depolarizations averaged 35 mv. Maximum rate of depolarization was 1–2 v/sec and the action potential duration varied from 250 milliseconds to much longer periods. Membrane reversal of up to 10 mv sometimes occurred. Total resistance decreased during depolarization and recovered during repolarization. Typical biphasic potentials were also recorded with extracellular electrodes. Their amplitude (peak to peak) varied from 0.3 to several millivolts and their duration (peak to peak) from 10–40 milliseconds. Reduction of external sodium concentration to as little as one-ninth normal (choline chloride or sucrose replacement) did not reduce the amplitudes of the resting or action potentials measured intracellularly or extracellularly, but decreased the action potential frequency. Membrane reversal still occurred with intracellular electrodes and the maximum rate of depolarization was unchanged. The rate of repolarization was increased so that the total duration of the action potential was 150 to 200 milliseconds. With extracellular electrodes, the peak to peak amplitudes were increased and the durations were unchanged. Further reduction of external sodium concentration to less than 15–20 meq/liter caused a contraction without further change in action potential configuration. Gradual relaxation and slowing of the repetition rate of action potentials occurred and resulted eventually in complete mechanical and electrical inactivity.Rabbit taenia coli were also studied and their electrical properties contrasted to those of cat myometrium. The conclusions were reached that: (1) the available evidence opposes the hypotheses that an inward sodium current accounts for depolarization in smooth muscle and (2) smooth muscles differed in their electrical properties and mechanisms of ion distribution not only from striate muscles but also from one another.

Membrane potentials in normal, isolated, perfused frog hearts.

Intracellular potentials from isolated normal frog hearts were measured in a series of 29 experiments, using microelectrodes of less than 1 micron tip diameter, a cathode follower input, direct coupled amplifier, and photographic registration of an oscilloscope trace. The perfusion fluid was Clark's solution, containing 1.08 mm calcium and 1.88 mm potassium. The average of 485 measurements of the normal resting potential was 84.5 mv. The average of 421 measurements of overshoot was 18.9 mv; and the average of 421 measurements of action potential was 102.5 mv. In eight experiments, including 141 values, the maximum depolarization rate was determined, using a graphical method of analysis. The average maximum upstroke velocity was 33.9 v/sec. The voltage-time curve of the action potential during the repolarization sequence showed considerable variation from fiber to fiber, but in most cases some evidence of a ‘spike’ component was seen.