scholarly journals Effects of Epinephrine on the Pacemaker Potassium Current of Cardiac Purkinje Fibers

1974 ◽  
Vol 64 (3) ◽  
pp. 293-319 ◽  
Author(s):  
Richard W. Tsien
Keyword(s):  
Potassium Current ◽  
Rate Coefficient ◽  
Dose Dependence ◽  
Pacemaker Activity ◽  
Maximal Effect ◽  
Activation Curve ◽  
Voltage Shift ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Order Of Magnitude

Epinephrine promotes spontaneous activity in cardiac Purkinje fibers through its action on the pacemaker potassium current (iKK2). The mechanism of the acceleratory effect was studied by means of a voltage clamp technique. The results showed that the hormone speeds the deactivation of iKK2 during pacemaker activity by displacing the kinetic parameters of iKK2 toward less negative potentials. This depolarizing voltage shift is the sole explanation of the acceleratory effect since epinephrine did not alter the rectifier properties of iKK2, or the underlying inward leakage current, or the threshold for iNNa. The dose dependence of the voltage shift in the iKK2 activation curve was similar in 1.8 and 5.4 mM [Ca]o. The maximal voltage shift (usually ∼20 mV) was produced by epinephrine concentrations of > 10-6 M. The half-maximal effect was evoked by 60 nM epinephrine, nearly an order of magnitude lower than required for half-maximal effect on the secondary inward current (Carmeliet and Vereecke, 1969). The ß-blocker propranolol (10-6 M) prevented the effect of epinephrine (10-7M) but by itself gave no voltage shift. Epinephrine shifted the activation rate coefficient α8 to a greater extent than the deactivation rate coefficient ß8, and often steepened the voltage dependence of the steady-state activation curve. These deviations from simple voltage shift behavior were discussed in terms of possible mechanisms of epinephrine's action on the iKK2 channel.

scholarly journals Mode of Action of Chronotropic Agents in Cardiac Purkinje Fibers

1974 ◽  
Vol 64 (3) ◽  
pp. 320-342 ◽  
Author(s):  
Richard W. Tsien
Keyword(s):  
Surface Charge ◽  
External Surface ◽  
Membrane Surface ◽  
Internal Surface ◽  
Phosphodiesterase Inhibitors ◽  
Common Mechanism ◽  
Pacemaker Activity ◽  
Response Curves ◽  
Voltage Shift ◽  
Cardiac Purkinje Fibers

Hauswirth et al. (1968) proposed that epinephrine acts on iKK2 by adding its own positive charge to the external membrane surface near the iKK2 channel. This hypothesis was tested by using noncationic compounds, theophylline and R07-2956, which mimicked epinephrine's effects on pacemaker activity and on iKK2. In maximally effective doses, theophylline or R07-2956 occluded the effect of epinephrine, indicating a shared final common mechanism. Since theophylline and R07-2956 are noncationic at pH 7.4, the common mechanism cannot be a direct change in external surface charge. On the contrary, epinephrine does not interfere with the voltage shift produced by La+++, which is thought to modify the external surface charge. The results argue against the original hypothesis but leave open the possibility that an alteration in internal surface charge generates the observed voltage shift. The potency of theophylline and R07-2956 as phosphodiesterase inhibitors suggests that the final common mechanism begins with the elevation of intracellular cyclic AMP, leading to a saturable process which limits the voltage shift's magnitude. This hypothesis is used to generate dose-response curves describing the combined effects of epinephrine and theophylline, and these are compared with experimental data.

The effect of raised pH on pacemaker activity and ionic currents in cardiac purkinje fibers

1978 ◽  
Vol 375 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Pierre-Paul van Bogaert ◽  
Johan S. Vereecke ◽  
Edward E. Carmeliet
Keyword(s):  
Ionic Currents ◽  
Pacemaker Activity ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers

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 Electrogenic sodium extrusion in cardiac Purkinje fibers.

1979 ◽  
Vol 73 (6) ◽  
pp. 819-837 ◽  
Author(s):  
D C Gadsby ◽  
P F Cranefield
Keyword(s):  
Sodium Pump ◽  
Pump Current ◽  
Flow Chamber ◽  
Resting Potential ◽  
Pacemaker Activity ◽  
Free Fluid ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Fast Flow ◽  
K Depletion

Thin canine cardiac Purkinje fibers in a fast flow chamber were exposed to K-free fluid for 15 s to 6 min to initiate "sodium loading," then returned to K-containing fluid to stimulate the sodium pump. The electrophysiological effects of enhanced pump activity may result from extracellular K depletion caused by enhanced cellular uptake of K or from an increase in the current generated as a result of unequal pumped movements of Na and K, or from both. The effects of pump stimulation were therefore studied under three conditions in which lowering the external K concentration ([K]0) causes changes opposite to those expected from an increase in pump current. First, the resting potential of Purkinje fibers may have either a "high" value of a "low" (less negative) value: at the low level of potential, experimental reduction of [K]0 causes depolarization, whereas an increase in pump current should cause hyperpolarization. Second, in regularly stimulated Purkinje fibers, lowering [K]0 prolongs the action potential, whereas an increase in outward pump current should shorten it. Finally, lowering [K]0 enhances spontaneous "pacemaker" activity in Purkinje fibers, whereas an increase in outward pump current should reduce or abolish spontaneous activity. Under all three conditions, we find that the effects of temporary stimulation of the sodium pump are those expected from a transient increase in outward pump current, not those expected from K depletion.

Differential Effects of Halothane and Isoflurane on Contractile Force and Calcium Transients in Cardiac Purkinje Fibers

1994 ◽  
Vol 80 (6) ◽  
pp. 1360-1368 ◽  
Author(s):  
David F. Stowe ◽  
Juraj Sprung ◽  
Lawrence A. Turner ◽  
John P. Kampine ◽  
Zeljko J. Bosnjak
Keyword(s):  
Contractile Force ◽  
Calcium Transients ◽  
Purkinje Fibers ◽  
Differential Effects ◽  
Cardiac Purkinje Fibers
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