Outward current and repolarization in hypoxic rat myocardium

1983 ◽  
Vol 244 (3) ◽  
pp. H341-H350
Author(s):  
C. H. Conrad ◽  
R. G. Mark ◽  
O. H. Bing

We studied the effects of brief periods (20-30 min) of hypoxia in the presence of 5 and 50 mM glucose and of glycolytic blockade (10(-4) M iodoacetic acid, IAA) on action potentials, membrane currents, and mechanical activity in rat ventricular papillary muscles using a single sucrose gap voltage-clamp technique. Steady-state outward current (iss) was determined at the end of a 500-ms clamp to the test potential following a 600-ms clamp to a holding potential of -50 mV. In the presence of 5 mM glucose, hypoxia resulted in a decrease in action potential duration (APD) and an increase in iss (on the order of 60% at 0 mV) over the potential range studied. The increase in iss did not appear to be due to an increase in leakage current or to a change in the cable properties of the preparation. Addition of 50 mM glucose prevented the change in both APD and iss with hypoxia. In addition, glycolytic blockade with IAA did not alter iss in the presence of oxygen. We conclude that an increase in iss appears to be a major factor in the abbreviation of rat ventricular action potential seen with hypoxia. Glycolysis appears to be a sufficient (with 50 mM glucose) but not necessary source of energy for the maintenance of normal iss.

1994 ◽  
Vol 267 (3) ◽  
pp. H1157-H1166 ◽  
Author(s):  
G. M. Wahler ◽  
S. J. Dollinger ◽  
J. M. Smith ◽  
K. L. Flemal

The rat ventricular action potential shortens after birth. The contribution of increases in the transient outward current (Ito) to postnatal action potential shortening was assessed by measuring Ito in isolated cells and by determining the effect of 2 mM 4-aminopyridine (4-AP) on the action potentials of papillary muscles. 4-AP had no effect on 1-day action potential duration at 25% repolarization (APD25), and 1-day cells had little Ito. In 8- to 10-day muscles, 4-AP caused a small, but significant, increase in APD25. Ito increased slightly between day 1 and days 8-10, but this increase was not significant. Most of the increase in Ito (79%) and in the response to 4-AP (64%) occurred between days 8-10 and adult; however, approximately 75% of the APD25 shortening took place by days 8-10. Thus, while Ito may contribute to repolarization in late neonatal and adult cells, the different time courses of action potential shortening and increases in Ito suggest that changes in Ito are unlikely to be responsible for most of the postnatal action potential shortening.


1986 ◽  
Vol 251 (2) ◽  
pp. H297-H306 ◽  
Author(s):  
R. F. Gilmour ◽  
J. J. Salata ◽  
J. R. Davis

Canine cardiac Purkinje fibers and atrial trabeculae and rat and cat papillary muscles superfused with a hyperkalemic, hypoxic, and acidotic Tyrode solution were depolarized to membrane potentials (-70 to -60 mV) at which action potential amplitude declined as the coupling intervals of pacing stimuli were prolonged from 500 to 4,500 ms. The rate-related decline of action potential amplitude appeared to be due to time-dependent recovery of the early outward current rather than to a decrease in inward calcium current, since it was prevented by 4-aminopyridine (1.0 mM), but not by isoproterenol (1.0 microM), caffeine (5.0 mM), or CsCl (5-20 mM) and it was accompanied by an exponential increase of developed tension. Experiments using Purkinje fibers mounted in a single sucrose gap chamber demonstrated that the rate-related decline of action potential amplitude was maximal at membrane potentials between -70 and -40 mV and was negligible at less negative or more negative membrane potentials. These results may pertain to the mechanism for deceleration-dependent bundle branch block.


1991 ◽  
Vol 66 (3) ◽  
pp. 744-761 ◽  
Author(s):  
S. M. Johnson ◽  
P. A. Getting

1. The purpose of this study was to determine the electrophysiological properties of neurons within the region of the nucleus ambiguus (NA), an area that contains the ventral respiratory group. By the use of an in vitro brain stem slice preparation, intracellular recordings from neurons in this region (to be referred to as NA neurons, n = 235) revealed the following properties: postinhibitory rebound (PIR), delayed excitation (DE), adaptation, and posttetanic hyperpolarization (PTH). NA neurons were separated into three groups on the basis of their expression of PIR and DE: PIR cells (58%), DE cells (31%), and Non cells (10%). Non cells expressed neither PIR nor DE and no cells expressed both PIR and DE. 2. PIR was a transient depolarization that produced a single action potential or a burst of action potentials when the cell was released from hyperpolarization. In the presence of tetrodotoxin (TTX), the maximum magnitude of PIR was 7-12 mV. Under voltage-clamp conditions, hyperpolarizing voltage steps elicited a small inward current during the hyperpolarization and a small inward tail current on release from hyperpolarization. These currents, which mediate PIR, were most likely due to Q-current because they were blocked with extracellular cesium and were insensitive to barium. 3. DE was a delay in the onset of action potential firing when cells were hyperpolarized before application of depolarizing current. When cells were hyperpolarized to -90 mV for greater than or equal to 300 ms, maximum delays ranged from 150 to 450 ms. The transient outward current underlying DE was presumed to be A-current because of the current's activation and inactivation characteristics and its elimination by 4-aminopyridine (4-AP). 4. Adaptation was examined by applying depolarizing current for 2.0 s and measuring the frequency of evoked action potentials. Although there was a large degree of variability in the degree of adaptation, PIR cells tended to express less adaptation than DE and Non cells. Nearly three-fourths of all NA neurons adapted rapidly (i.e., 50% adaptation in less than 200 ms), but PIR cells tended to adapt faster than DE and Non cells. PTH after a train of action potentials was relatively rare and occurred more often in DE cells (43%) and Non cells (33%) than in PIR cells (13%). PTH had a magnitude of up to 18 mV and time constants that reflected the presence of one (1.7 +/- 1.4 s, mean +/- SD) or two components (0.28 +/- 0.13 and 4.1 +/- 2.2 s).(ABSTRACT TRUNCATED AT 400 WORDS)


1988 ◽  
Vol 255 (5) ◽  
pp. H992-H999 ◽  
Author(s):  
R. Mohabir ◽  
G. R. Ferrier

The inducibility of slow-response automaticity was assessed during ischemic conditions and reperfusion by application of extracellular current. Isolated canine Purkinje fibers were depolarized to membrane potentials less than -65 mV to elicit depolarization-induced automaticity (DIA). Ischemic conditions increased the cycle length of DIA and, in some tissues, prevented sustained DIA or completely abolished DIA. The magnitude of depolarization required to elicit DIA also increased. Inhibition of DIA occurred at a time when action potential plateaus were abbreviated. The effect of reperfusion on DIA was biphasic. Initial reappearance of DIA was followed by inhibition and reduction of the membrane potential range over which DIA could be elicited. Plateaus of action potentials initiated at high membrane potential were abbreviated at this time. DIA returned again as reperfusion effects dissipated. Phasic changes in the inducibility of DIA may represent changes in availability of the slow inward current and may regulate the timing and types of arrhythmic activity occurring with ischemia and reperfusion.


1984 ◽  
Vol 62 (5) ◽  
pp. 596-599
Author(s):  
Julio Alvarez ◽  
Francisco Dorticós ◽  
Jesús Morlans

Experiments were performed to study the effects of hypoxia on the characteristics of premature action potentials of rabbit papillary muscles. At normal resting potential, the duration of the premature action potential at the shortest coupling intervals was always greater than that of the control response. As the coupling interval was increased beyond 150 ms, the duration of the premature action potential regained control values. In cells depolarized to −70 mV by KCl, early lengthening of the premature response was attenuated. After 60 min of hypoxia, recovery of action potential duration at normal and reduced resting potentials was accelerated. The maximum rate of depolarization and its reactivation time constant were not affected by 60 min of hypoxia. It is suggested that intracellular free Ca is important in the control of action potential duration via the outward background potassium current.


1971 ◽  
Vol 57 (3) ◽  
pp. 290-296 ◽  
Author(s):  
Gerhard Giebisch ◽  
Silvio Weidmann

Bundles of sheep ventricular fibers were voltage-clamped utilizing a modified sucrose gap technique and intracellular voltage control. An action potential was fired off in the usual way, and the clamp circuit was switched on at preselected times during activity. Clamping the membrane back to its resting potential during the early part of an action potential resulted in a surge of inward current. The initial amplitude of this current surge decreased as the clamp was switched on progressively later during the action potential. Inward current decreasing as a function of time was also recorded if the membrane potential was clamped beyond the presumed K equilibrium potential (to -130 mv). Clamping the membrane to the inside positive range (+40 mv to +60 mv) at different times of an action potential resulted in a step of outward current which was not time-dependent. The results suggest that normal repolarization of sheep ventricle depends on a time-dependent decrease of inward current (Na, Ca) rather than on a time-dependent increase of outward current (K).


2000 ◽  
Vol 83 (3) ◽  
pp. 1253-1263 ◽  
Author(s):  
Fivos Vogalis ◽  
Kirk Hillsley ◽  
Terence K. Smith

The aim of this study was to perform a patch-clamp analysis of myenteric neurons from the guinea pig proximal colon. Neurons were enzymatically dispersed, cultured for 2–7 days, and recorded from using whole cell patch clamp. The majority of cells fired phasically, whereas about one-quarter of the neurons fired in a tonic manner. Neurons were divided into three types based on the currents activated. The majority of tonically firing neurons lacked an A-type current, but generated a large fast transient outward current that was associated with the rapid repolarizing phase of an action potential. The fast transient outward current was dependent on calcium entry and was blocked by tetraethylammonium. Cells that expressed both an A-type current and a fast transient outward current were mostly phasic. Depolarization of these cells to suprathreshold potentials from less than −60 mV failed to trigger action potentials, or action potentials were only triggered after a delay of >50 ms. However, depolarizations from more positive potentials triggered action potentials with minimal latency. Neurons that expressed neither the A-type current or the fast transient outward current were all phasic. Sixteen percent of neurons were similar to AH/type II neurons in that they generated a prolonged afterhyperpolarization following an action potential. The current underlying the prolonged afterhyperpolarization showed weak inward rectification and had a reversal potential near the potassium equilibrium potential. Thus cultured isolated myenteric neurons of the guinea pig proximal colon retain many of the diverse properties of intact neurons. This preparation is suitable for further biophysical and molecular characterization of channels expressed in colonic myenteric neurons.


1979 ◽  
Vol 81 (1) ◽  
pp. 93-112
Author(s):  
R. W. Meech

Membrane potential oscillations can be induced in molluscan neurones under a variety of artificial conditions. In the so-called ‘burster’ neurones oscillations are generated even in isolated cells. A likely mechanism for ‘bursting’ involves the following ionic currents: 1. A transient inward current carried by Na+ and Ca2+. This current is responsible for the upstroke of the action potentials. 2. A delayed outward current carried by K+. This current is voltage-sensitive and is responsible for the downstroke of the action potential during the early part of the burst. It becomes progressively inactivated during the burst. Its amplitude depends on the intracellular pH. 3. A rapidly developing outward current carried by K+ which is inactivated at potentials close to action potential threshold. This current tends to hold the membrane in the hyperpolarized state and is involved in spacing the action potentials. 4. A prolonged inward current which may not inactivate. It is probably carried by both Na+ and Ca2+. This current is responsible for the depolarizing phase of the burst but also contributes to the action potential. 5. A slowly developing outward current, carried by K+. This current appears as a result of a slow increase in intracellular ionized calcium and is responsible for the hyperpolarizing phase of the burst. Note that a transient increase in this current may also contribute to the falling phase of the action potential during the later stages of the burst. It is also sensitive to intracellular pH. One of the more significant features of this system of producing membrane potential oscillations is that the frequency of the bursts depends on the rate at which the intracellular ionized calcium returns to its resting level. This process depends on the metabolic state of the animal which can thereby exert a considerable influence on the electrical activity of burster neurones.


2000 ◽  
Vol 279 (1) ◽  
pp. H397-H421 ◽  
Author(s):  
H. Zhang ◽  
A. V. Holden ◽  
I. Kodama ◽  
H. Honjo ◽  
M. Lei ◽  
...  

Mathematical models of the action potential in the periphery and center of the rabbit sinoatrial (SA) node have been developed on the basis of published experimental data. Simulated action potentials are consistent with those recorded experimentally: the model-generated peripheral action potential has a more negative takeoff potential, faster upstroke, more positive peak value, prominent phase 1 repolarization, greater amplitude, shorter duration, and more negative maximum diastolic potential than the model-generated central action potential. In addition, the model peripheral cell shows faster pacemaking. The models behave qualitatively the same as tissue from the periphery and center of the SA node in response to block of tetrodotoxin-sensitive Na+current, L- and T-type Ca2+ currents, 4-aminopyridine-sensitive transient outward current, rapid and slow delayed rectifying K+ currents, and hyperpolarization-activated current. A one-dimensional model of a string of SA node tissue, incorporating regional heterogeneity, coupled to a string of atrial tissue has been constructed to simulate the behavior of the intact SA node. In the one-dimensional model, the spontaneous action potential initiated in the center propagates to the periphery at ∼0.06 m/s and then into the atrial muscle at 0.62 m/s.


1974 ◽  
Vol 63 (2) ◽  
pp. 257-278 ◽  
Author(s):  
Joseph Bastian ◽  
Shigehiro Nakajima

The double sucrose-gap method was applied to single muscle fibers of Xenopus. From the "artificial node" of the fiber, action potentials were recorded under current-clamping condition together with twitches of the node. The action potentials were stored on magnetic tape. The node was then made inexcitable by tetrodotoxin or by a sodium-free solution, and the wave form of the action potential stored on magnetic tape was imposed on the node under voltage-clamp condition (simulated AP). The twitch height caused by the simulated AP's was always smaller than the twitch height produced by the real action potentials, the ratio being about 0.3 at room temperature. The results strongly suggest that the transverse tubular system is excitable and is necessary for the full activation of twitch, and that the action potential of the tubules contributes to about 70 % of the total mechanical output of the normal isotonic twitch at 20°C. Similar results were obtained in the case of tetanic contraction. At a temperature near 10°C, twitches produced by the simulated AP were not very different (85 % of control amplitude) from the twitches caused by real action potentials. This indicates that the excitability of the tubules becomes less necessary for the full activation of twitch as the temperature becomes lower.


Sign in / Sign up

Export Citation Format

Share Document