scholarly journals Excitation-contraction coupling in cardiac Purkinje fibers. Effects of caffeine on the intracellular [Ca2+] transient, membrane currents, and contraction.

1984 ◽  
Vol 83 (3) ◽  
pp. 417-433 ◽  
Author(s):  
P Hess ◽  
W G Wier
Keyword(s):  
Steady State ◽  
Time Course ◽  
Positive Inotropic Effect ◽  
Outward Current ◽  
Membrane Currents ◽  
Slow Inward Current ◽  
Transient Outward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
L1 And L2

The effects of caffeine on tension, membrane potential, membrane currents, and intracellular [Ca2+], measured as the light emitted by the Ca2+-activated photoprotein aequorin, were studied in canine cardiac Purkinje fibers. An initial, transient, positive inotropic effect of caffeine was accompanied by a transient increase in the second component of the aequorin signal (L2) but not the first (L1). In the steady state, 4 or 10 mM caffeine always decreased twitch tension and greatly reduced both L1 and L2. At a concentration of 2 mM, caffeine usually reduced but occasionally increased the steady state twitch tension. However, 2 mM caffeine always reduced both L1 and L2. Caffeine eliminated the diastolic oscillations of intracellular [Ca2+] induced by high extracellular [Ca2+]. In voltage-clamp experiments, 10 mM caffeine reduced the transient outward current and the peak tension elicited by step depolarization from a holding potential of -45 mV. In the presence of 20 mM Cs+, 10 mM caffeine reduced slow inward current. However, the time course of this reduction was far slower than that in tension and light observed in separate experiments. The simplest explanation of the results is that caffeine inhibits the sequestration of Ca2+ by the sarcoplasmic reticulum. The results also suggest that in Purkinje fibers caffeine increases the sensitivity of the myofilaments to Ca2+.

scholarly journals Properties of "creep currents" in single frog atrial cells.

1986 ◽  
Vol 87 (6) ◽  
pp. 833-855 ◽  
Author(s):  
J R Hume ◽  
A Uehara
Keyword(s):  
Time Course ◽  
Outward Current ◽  
Membrane Current ◽  
K Channel ◽  
Transient Outward Current ◽  
Ca Channel ◽  
Purkinje Fibers ◽  
Atrial Cells ◽  
Cardiac Purkinje Fibers ◽  
Inward Currents

Changes in membrane current in response to an elevation of [Na]i were studied in enzymatically dispersed frog atrial cells. Na loading by either intracellular dialysis or exposure to the Na ionophore monensin produces changes in membrane current that resemble the "creep currents" originally observed in cardiac Purkinje fibers during exposure to low-K solutions. Na loading induces a transient outward current during depolarizing voltage-clamp pulses, followed by an inward current in response to repolarization back to the holding potential. In contrast to cardiac Purkinje fibers, Na loading of frog atrial cells induces creep currents without accompanying transient inward currents. Creep currents induced by Na loading are insensitive to K channel antagonists like Cs and 4-aminopyridine; they are not influenced by doses of Ca channel antagonists that abolish iCa, but are sensitive to changes in [Ca]o or [Na]o. A comparison of the time course of development of inward creep currents are not tail currents associated with iCa. Inward creep currents can also be induced by experimental interventions that increase the iCa amplitude. Exposure to isoproterenol enhances the iCa amplitude and induces inward creep currents; both can be attenuated by Ca channel antagonists. Both inward and outward creep currents are blocked by low doses of La, independently of La's ability to block iCa. It is concluded that (a) creep currents are not mediated by voltage-gated Na, Ca, or K channels or by an electrogenic Na,K pump; (b) inward creep currents induced either by Na loading or in response to an increase in the amplitude of iCa are triggered by an elevation of [Ca]i; and (c) creep currents may be generated by either an electrogenic Na/Ca exchange mechanism or by a nonselective cation channel activated by [Ca]i.

Membrane currents, contractions, and aftercontractions in cardiac Purkinje fibers

1982 ◽  
Vol 243 (1) ◽  
pp. H77-H86 ◽  
Author(s):  
S. L. Lipsius ◽  
W. R. Gibbons
Keyword(s):  
Outward Current ◽  
Membrane Conductance ◽  
Isometric Tension ◽  
Membrane Current ◽  
Membrane Currents ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
And Behavior ◽  
Normal Calcium ◽  
Current Behavior

We examined relationships between isometric tension and membrane currents in sheep Purkinje fibers voltage clamped by the two-microelectrode method. Oscillatory restitution of contractility was accompanied by a small oscillation in membrane current and by an aftercontraction. The membrane current oscillation resembled the transient inward current (TI) others have reported in the presence of strophanthidin. Twitches produced by voltage clamp depolarizations did not correlate with net outward current in normal solution, but when the early outward current was blocked by 0.5 mM 4-aminopyridine, the residual outward current did correlate with twitches elicited by strong depolarizing clamps, particularly in solutions containing higher than normal calcium concentrations. The results illustrate important similarities and differences between membrane current behavior in sheep Purkinje fibers and behavior others have reported in calf fibers. Correlations between restitution, aftercontractions, and TI's, and between twitch tension and a component of outward current, may arise because of calcium regulation of membrane conductance, electrogenic Na-Ca exchange, or a combination of these and other mechanisms.

Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers

1985 ◽  
Vol 249 (1) ◽  
pp. H122-H132
Author(s):  
J. M. Jaeger ◽  
W. R. Gibbons
Keyword(s):  
Action Potential ◽  
Outward Current ◽  
Purkinje Fiber ◽  
Slow Inward Current ◽  
Channel Blockers ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Current Voltage ◽  
Current Voltage Relation

We have tried to answer two fundamental questions concerning the outward current IX1 of cardiac Purkinje fibers. 1) Is it possible that current changes identified as arising from IX1 in voltage-clamp experiments are actually manifestations of changes in the slow inward current (Isi); and 2) is IX1 in fact required to produce the electrical phenomena attributed to it? Isi behavior and the role of IX1 were explored using computer simulation. The Isi model produced current changes during depolarizations and hyperpolarizations from depolarized resting potentials like those attributed to IX1. It also produced a component of "tail currents" that behaved like IX1. If these current changes were analyzed, assuming that an outward current is responsible, the resulting kinetics and current voltage relation would be very similar to the kinetics and current voltage relation reported for IX1. Using the McAllister, Noble, and Tsien formulation of the Purkinje fiber action potential, we found that IX1 is not essential for repolarization of the reconstructed action potential nor is it needed to reproduce interval duration effects and the effects of applied current in that model. Data suggesting that calcium channel blockers reduce IX1 and that catecholamines increase IX1 may be explained as arising from changes in Isi. Thus many manifestations of IX1 can be explained as arising from unanticipated behavior of Isi, and IX1 does not necessarily play a key role in generating Purkinje fiber electrical activity.

scholarly journals Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization: experiments in sodium-free bathing media.

1977 ◽  
Vol 70 (2) ◽  
pp. 149-169 ◽  
Author(s):  
C M Baumgarten ◽  
G Isenberg ◽  
T F McDonald ◽  
R E Ten Eick
Keyword(s):  
Membrane Potential ◽  
Voltage Clamp ◽  
Driving Force ◽  
Time Course ◽  
Potassium Concentration ◽  
Outward Current ◽  
Voltage Step ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Voltage Dependent

Voltage clamp hyperpolarization and depolarization result in currents consistent with depletion and accumulation of potassium in the extracellular clefts o cardiac Purkinje fibers exposed to sodium-free solutions. Upon hyperpolarization, an inward current that decreased with time (id) was observed. The time course of tail currents could not be explained by a conductance exhibiting voltage-dependent kinetics. The effect of exposure to cesium, changes in bathing media potassium concentration and osmolarity, and the behavior of membrane potential after hyperpolarizing pulses are all consistent with depletion of potassium upon hyperpolarization. A declining outward current was observed upon depolarization. Increasing the bathing media potassium concentration reduced the magnitude of this current. After voltage clamp depolarizations, membrane potential transiently became more positive. These findings suggest that accumulation of potassium occurs upon depolarization. The results indicate that changes in ionic driving force may be easily and rapidly induced. Consequently, conclusions based on the assumption that driving force remains constant during the course of a voltage step may be in error.

Effects of myocardial hypertrophy on transient outward current

1994 ◽  
Vol 266 (5) ◽  
pp. H1738-H1745 ◽  
Author(s):  
Q. Li ◽  
E. C. Keung
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Time Course ◽  
Myocardial Hypertrophy ◽  
Pressure Overload ◽  
Reversal Potential ◽  
Outward Current ◽  
Transient Outward Current ◽  
The Difference

In the one-clip, two-kidney model of hypertensive rat, a gradual chronic pressure overload is imposed on the heart. Myocardial hypertrophy resulting from such pressure overload is associated with an increased but slower inactivating L-type calcium current and prolongation of action potential duration. Voltage clamp experiments in a variety of excitable tissues indicate that a 4-aminopyridine-sensitive transient outward current (Ito) plays an important role in regulating the action potential duration. Accordingly, we studied Ito in single adult cardiac myocytes enzymatically isolated from hypertrophied left ventricles of the renovascular hypertensive (HBP) rat hearts using the whole cell patch-clamp method. The current densities (normalized to cell capacitative surface area) measured at the early transient peak Ito, at the steady state, and as the difference between the transient peak and the steady state were larger in HBP cells (n = 23) than in control (Ctrl) cells (n = 20) (P < 0.05). There was no difference in the Ito reversal potential between Ctrl (-60.9 +/- 1.9 mV, mean +/- SE; n = 16) and HBP (-63.7 +/- 2.6 mV; n = 19) cells. The observed increase in Ito amplitude was not due to an increase in the number of channels available for activation or in the fraction of channels activated because there were no statistical differences in the membrane potential at which one-half of the Ito channels are activated (V0.5) for the steady-state activation and inactivation curves between Ctrl and HBP cells. The time course of inactivation of Ito was described by a double-exponential function.(ABSTRACT TRUNCATED AT 250 WORDS)

Cycle length-dependent action potential duration in canine cardiac Purkinje fibers

1984 ◽  
Vol 247 (6) ◽  
pp. H936-H945 ◽  
Author(s):  
V. Elharrar ◽  
H. Atarashi ◽  
B. Surawicz
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Cycle Length ◽  
Slow Inward Current ◽  
Tetraethylammonium Chloride ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Kinetics Of

We studied the effects of pharmacologic probes that affect predominantly the Na inward current [tetrodotoxin (TTX), lidocaine], the slow inward current [cobalt, isoproterenol, verapamil], and the potassium currents [tetraethylammonium chloride (TEA), SG-75] on the duration of the action potential (APD) of canine cardiac Purkinje fibers during steady state and restitution. A schema is proposed in which the APD during steady state or restitution is determined by three factors: maximum action potential duration (APDmax), kinetics of restitution, and “memory.” The predicted APDmax was 469 +/- 34 (SE) ms (n = 27) in control. It was prolonged (P less than 0.05) by cobalt, verapamil, and TEA and shortened (P less than 0.05) by TTX, lidocaine, isoproterenol, and SG-75. In control, the kinetics of restitution were described by a sum of two exponentials with time constant T1 = 137 +/- 9 ms and T2 = 1,665 +/- 135 ms (n = 27), respectively. T1 was prolonged (P less than 0.05) by TTX, lidocaine, and verapamil but was not changed by other probes. None of the probes studied altered the T2 of restitution or the memory factor, computed at a cycle length of 500 ms from the predicted APDmax and the plateau of restitution. Low temperature (31 degrees C) prolonged APDmax and T1 and reduced the memory. We conclude that each of the proposed three factors is controlled by different mechanisms and that a TTX-sensitive current appears to contribute to the process of restitution of APD.

Oscillation of Membrane Currents During the Action Potential in Chara corallina: Modification and Significance for Repolarisation of the Membrane Potential and Salt Sensitivity

1996 ◽  
Vol 23 (3) ◽  
pp. 361
Author(s):  
J.I Kourie
Keyword(s):  
Time Course ◽  
Outward Current ◽  
Chara Corallina ◽  
Membrane Currents ◽  
Inactivation Kinetics ◽  
Transient Outward Current ◽  
Voltage Dependent ◽  
Current Activation ◽  
K Current ◽  
Kinetics Of

Depolarising voltage-clamp steps in C. corallina induced membrane currents which differ from those of C. inflata in two aspects: (1) The absence of a 'hump', i.e. a transient outward current,Io(max) which is present in C. inflata, and (2) the presence in C, corallina of a voltage-dependent current oscillation, i.e. a succession of decaying peaks. The peaks of the oscillating transient inward current, Ii(max), were voltage dependent and sensitive to block with 9-anthracenecarboxylic acid (9-AC). The oscillating current is carried by C1- and its time course is determined by the activation and inactivation kinetics of C1- channels. Extracellular NaCl delayed current activation, induced a voltage-dependent increase in Ii(max) and a decrease in the steady-state outward K+ current, Is. NaCl increased the occurrence of oscillation and enhanced the amplitude of the oscillating current. Extracellular sorbitol induced an overall reduction in Ii(max) and had virtually no effect on Is. I suggest that the enhancement of the oscillating transient inward CI- current, Ii(max), by NaCl is due to ionic effects of NaCl rather than to its osmotic effects.

Alpha 1-adrenoceptor subtypes mediating inotropic and electrophysiological effects in mammalian myocardium

1996 ◽  
Vol 271 (4) ◽  
pp. H1423-H1432
Author(s):  
M. Nagashima ◽  
Y. Hattori ◽  
Y. Akaishi ◽  
N. Tohse ◽  
I. Sakuma ◽  
...  
Keyword(s):  
Positive Inotropic Effect ◽  
Outward Current ◽  
Ventricular Myocardium ◽  
Inotropic Effect ◽  
Transient Outward Current ◽  
Papillary Muscles ◽  
Binding Studies ◽  
Positive Inotropism ◽  
Wb 4101 ◽  
Rabbit Ventricular Myocardium

Stimulation of alpha 1-adrenoceptors produces a positive inotropic effect in rat and rabbit ventricular myocardium via different mechanisms, the prolongation of action potential duration (APD) exclusively in the former and an increase in myofibrillar Ca2+ sensitivity in large part in the latter. This study was designed to determine whether the two inotropic mechanisms are mediated by different alpha 1-adrenoceptor subtypes. In rat papillary muscles, the positive inotropic effect and APD prolongation induced by phenylephrine (in the presence of propranolol) were inhibited by WB-4101, but not affected by chlorethylclonidine (CEC). WB-4101, but not CEC, blocked the phenylephrine-induced inhibition of the transient outward current (Ito) in rat ventricular cells. On the other hand, WB-4101 and CEC each antagonized the positive inotropic effect of phenylephrine in rabbit papillary muscles. However, the phenylephrine-induced APD prolongation observed in rabbit papillary muscles was blocked only by WB-4101. These results indicate that the WB-4101 sensitive alpha 1-adrenoceptor subtype mediates the positive inotropism that is correlated with the APD prolongation resulting from Ito reduction, whereas the CEC-sensitive subtype mediates the positive inotropism that is probably associated with increased myofibrillar Ca2+ sensitivity. Radioligand binding studies with [3H] prazosin showed a similar ratio of alpha 1A-to alpha 1B-adrenoceptor subtypes in rat and rabbit ventricular myocardium, implying that the different degree of contribution of each action mechanism to the overall inotropic effect in the two species cannot be explained by distribution of the alpha 1-adrenoceptor subtypes.

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