scholarly journals Effects of caffeine, tetracaine, and ryanodine on calcium-dependent oscillations in sheep cardiac Purkinje fibers.

1985 ◽  
Vol 86 (6) ◽  
pp. 877-889 ◽  
Author(s):  
C J Nieman ◽  
D A Eisner
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Oscillation Amplitude ◽  
Membrane Current ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Calcium Dependent ◽  
Cardiac Purkinje Fibers ◽  
High Concentrations

Membrane current and tension were measured in voltage-clamped sheep cardiac Purkinje fibers. Elevating the intracellular calcium concentration ([Ca2+]i) results in oscillations of membrane current and tension both at rest and during stimulation. During stimulation, an oscillatory transient inward current and an after contraction follow repolarization. We have examined the effects on the oscillations of changing the extracellular calcium concentration ([Ca2+]o) and of adding various drugs. In agreement with previous work, high concentrations of drugs that affect the sarcoplasmic reticulum, namely caffeine (10-20 mM), tetracaine (1 mM), and ryanodine (10 microM), abolish the oscillations. However, at lower concentrations, these three drugs have different effects on the oscillations. Caffeine (1-2 mM) decreases the oscillation amplitude but increases the frequency. Tetracaine (100-500 microM) has little effect on the magnitude of the oscillations but decreases their frequency. Ryanodine, at all concentrations used (0.1-10 microM), eventually abolishes the oscillations but, in doing so, decreases the magnitude, leaving the frequency unaffected. When [Ca2+]o was changed in order to vary [Ca2+]i, both the frequency and the magnitude of the oscillations always changed in the same direction. This suggests that these three drugs have effects in addition to just changing [Ca2+]i.

scholarly journals Calcium- and voltage-activated plateau currents of cardiac Purkinje fibers.

1987 ◽  
Vol 89 (6) ◽  
pp. 921-958 ◽  
Author(s):  
J L Kenyon ◽  
J L Sutko
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Intracellular Calcium ◽  
Potassium Current ◽  
Calcium Release ◽  
Outward Current ◽  
Calcium Transient ◽  
Chloride Ions ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Sarcoplasmic Reticulum Calcium

We have used the two-microelectrode voltage-clamp technique to investigate the components of membrane current that contribute to the formation of the early part of the plateau phase of the action potential of calf cardiac Purkinje fibers. 3,4-Diaminopyridine (50 microM) reduced the net transient outward current elicited by depolarizations to potentials positive to -30 mV but had no consistent effect on contraction. We attribute this effect to the blockade of a voltage-activated transient potassium current component. Ryanodine (1 microM), an inhibitor of sarcoplasmic reticulum calcium release and intracellular calcium oscillations in Purkinje fibers (Sutko, J.L., and J.L. Kenyon. 1983. Journal of General Physiology. 82:385-404), had complex effects on membrane currents as it abolished phasic contractions. At early times during a depolarization (5-30 ms), ryanodine reduced the net outward current. We attribute this effect to the loss of a component of calcium-activated potassium current caused by the inhibition of sarcoplasmic reticulum calcium release and the intracellular calcium transient. At later times during a depolarization (50-200 ms), ryanodine increased the net outward current. This effect was not seen in low-sodium solutions and we could not observe a reversal potential over a voltage range of -100 to +75 mV. These data suggest that the effect of ryanodine on the late membrane current is attributable to the loss of sodium-calcium exchange current caused by the inhibition of sarcoplasmic reticulum calcium release and the intracellular calcium transient. Neither effect of ryanodine was dependent on chloride ions, which suggests that chloride ions do not carry the ryanodine-sensitive current components. Strontium (2.7 mM replacing calcium) and caffeine (10 mM), two other treatments that interfere with sarcoplasmic reticulum function, had effects in common with ryanodine. This supports the hypothesis that the effects of ryanodine may be attributed to the inhibition of sarcoplasmic reticulum calcium release.

scholarly journals Slow inward current and contraction of sheep cardiac Purkinje fibers.

1975 ◽  
Vol 65 (3) ◽  
pp. 367-384 ◽  
Author(s):  
W R Gibbons ◽  
H A Fozzard
Keyword(s):  
Intracellular Calcium ◽  
Voltage Clamp ◽  
Mammalian Species ◽  
Slow Inward Current ◽  
Ventricular Muscle ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Rate Of Recovery ◽  
Calcium Pool

A "slow" inward current (Is) has been identified in ventricular muscle and Purkinje fibers of several mammalian species. The two-microelectrode voltage clamp technique is used to examine some of the relationships between Is and contraction of the sheep cardiac Purkinje fiber. "Tails" of inward current occurring on repolarization and extrapolation of Is recovery each show that the Is system may not inactivate completely during prolonged depolarization. The rate of recovery of Is after a depolarization is slow, and when a train of 300-ms clamps (frequency 1 s-1) is begun after a rest, Is is larger for the first clamp than it is for succeedings clamps. For the first clamp after a rest, the thresholds for Is and tension are the same and there is a direct correlation between peak tension and peak Is for clamp voltages between threshold and minus 40 mV. After a clamp, however, the ability to contract recovers much more slowly than does Is. Therefore, since Is may occur under certain conditions without tension, the realtionship between Is and tension must be indirect. Calcium entering the cell via this current may replenish or augment an intracellular calcium pool.

Injection of inositol 1, 3, 4, 5-tetrakisphosphate into Xenopus oocytes generates a chloride current dependent upon intracellular calcium

1987 ◽  
Vol 232 (1266) ◽  
pp. 59-70 ◽  
Keyword(s):  
Intracellular Calcium ◽  
Chloride Channels ◽  
Surface Membrane ◽  
Chelating Agent ◽  
Threshold Current ◽  
Inward Current ◽  
Inositol 1 ◽  
Calcium Dependent ◽  
Transient Inward Current ◽  
The Mean

Injection of inositol 1, 3, 4, 5-tetrakisphosphate (Ins(1, 3, 4, 5)P 4 ) into voltage-clamped oocytes of Xenopus laevis elicited an oscillatory chloride membrane current. This response did not depend upon extracellular calcium, because it could be produced in calcium-free solution and after addition of cobalt to block calcium channels in the surface membrane. However, it was abolished after intracellular loading with the calcium chelating agent EGTA, indicating a dependence upon intracellular calcium. The mean dose of Ins(1, 3, 4, 5)P 4 required to elicit a threshold current was 4 x 10 -14 mol. In comparison, inositol 1, 4, 5-trisphosphate (Ins(1, 4, 5)P 3 ) gave a similar oscillatory current with doses of about one twentieth as big. Hyperpolarization of the oocyte membrane during activation by Ins(1, 3, 4, 5)P 4 elicited a transient inward current, as a result of the opening of calcium-dependent chloride channels subsequent to the entry of external calcium. In some oocytes the injection of Ins(1, 3, 4, 5)P 4 was itself sufficient to allow the generation of the transient inward current, whereas in others a prior injection of Ins(1, 4, 5)P 3 was required. We conclude that Ins(1, 3, 4, 5)P 4 causes the release of intra­cellular calcium from stores in the oocyte, albeit with less potency than Ins(1, 4, 5)P 3 . In addition, Ins(1, 3, 4, 5)P 4 activates voltage-sensitive cal­cium channels in the surface membrane, via a process that may require ‘priming’ by Ins(1, 4, 5)P 3 .

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.

A re-examination of late outward plateau currents of cardiac Purkinje fibers

1985 ◽  
Vol 249 (1) ◽  
pp. H108-H121
Author(s):  
J. M. Jaeger ◽  
W. R. Gibbons
Keyword(s):  
Action Potential ◽  
Voltage Clamp ◽  
Critical Role ◽  
Membrane Current ◽  
Purkinje Fiber ◽  
Purkinje Fibers ◽  
Outward Currents ◽  
Cardiac Purkinje Fibers

Two outward currents, IX1 and IX2, are thought to be activated by depolarization of the Purkinje fiber. One of these, IX1, is presently believed to play a critical role in repolarization of the action potential. The IX currents were originally analyzed in voltage-clamp experiments in sheep Purkinje fibers. These experiments were designed to minimize interference by other currents, and it was assumed that changes of the net current were produced entirely by the IX currents. We have tried to repeat the original experiments and the analysis that led to acceptance of the existence and roles of the IX currents, without success. Moreover, tests of how membrane current should behave if the IX current hypothesis is correct did not give satisfactory results. Our data suggest the original conclusions about IX1 and IX2 may need substantial revision.

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.

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.

Role of calcium in caffeine-norepinephrine interactions in cardiac Purkinje fibers

1989 ◽  
Vol 257 (1) ◽  
pp. H226-H237 ◽  
Author(s):  
H. Satoh ◽  
M. Vassalle
Keyword(s):  
Calcium Concentration ◽  
Iodoacetic Acid ◽  
Slow Inward Current ◽  
Extracellular Potassium ◽  
Purkinje Fibers ◽  
Extracellular Potassium Concentration ◽  
Cardiac Purkinje Fibers ◽  
Ca Uptake

Caffeine-norepinephrine interactions were studied in canine cardiac Purkinje fibers perfused in vitro. Caffeine (0.5-1 mM) or theophylline (0.5-1 mM) increased and then decreased contractile force in the absence and presence of 0.5-10 microM norepinephrine (NE) [in high extracellular calcium concentration ([Ca]o) caffeine only decreases force]. Occasionally, caffeine only decreased force in the presence of NE. In the presence of NE and 12 mM (sometimes even 4 mM) extracellular potassium concentration, caffeine did not decrease force below the precaffeine level. Reciprocally, in 0.5-2 mM caffeine NE increased force, although less than in the absence of caffeine. Even in 9 mM caffeine, NE increased force but slowed the final phase three repolarization of the action potential. Both NE and 8.1 mM [Ca]o increased force, but NE decreased force in the presence of high [Ca]o. In NE and propranolol (or propranolol alone), caffeine only increased force, whereas it had the usual effects in the presence of methoxamine or phenotolamine. In the presence of iodoacetic acid and 2-deoxy-D-glucose, NE caused contracture and caffeine exaggerated it. In contrast, in NE and 2 mM Mn, caffeine only increased force. It is concluded that initially NE diminishes the cytoplasmic calcium overload induced by caffeine (by promoting Ca uptake into the sarcoplasmic reticulum) and subsequently enhances it (by increasing the slow inward current).

Spontaneous oscillations in cytoplasmic calcium concentration in vascular smooth muscle

1989 ◽  
Vol 256 (5) ◽  
pp. C951-C957 ◽  
Author(s):  
P. L. Weissberg ◽  
P. J. Little ◽  
A. Bobik
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Channel ◽  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Calcium Release ◽  
Extracellular Calcium ◽  
Fluorescence Measurement ◽  
Cytoplasmic Calcium ◽  
Spontaneous Oscillations

Fluorescence measurement of fura-2 and quin2 signals from confluent primary cultures of serum-deprived rat aortic smooth muscle cells have revealed spontaneous oscillations in intracellular calcium concentration ([Ca2+]i). The transients consist of a rapid increase in [Ca2+]i that averages 60 nM and lasts approximately 30 s. They are caused by intracellular calcium release and an influx of extracellular calcium. Exposure of cells to the calcium-channel antagonists verapamil and diltiazem or incubation in nominally calcium-free medium reduced both the duration and amplitude of the transients; in contrast, the calcium-channel agonist (-)BAY K 8644 increased their duration. The transients were abolished by caffeine and 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate, agents that interfere with calcium release from the sarcoplasmic reticulum. These findings demonstrate that the sarcoplasmic reticulum is a primary source for the spontaneous oscillations in cytoplasmic calcium and is closely associated with the influx of extracellular calcium. Although the function of these transients is unclear, they may be involved in the spontaneous contractions observed in some vessels and in the regulation of vascular resistance.

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