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
1974 ◽  
Vol 64 (3) ◽  
pp. 293-319 ◽  
Author(s):  
Richard W. Tsien

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.


1979 ◽  
Vol 73 (6) ◽  
pp. 819-837 ◽  
Author(s):  
D C Gadsby ◽  
P F Cranefield

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.


1979 ◽  
Vol 73 (2) ◽  
pp. 199-218 ◽  
Author(s):  
K W Spitzer ◽  
P M Hogan

Studies were performed on canine cardiac Purkinje fibers to evaluate the effects of acidosis and bicarbonate (HCO3) on action potential repolarization. Extracellular pH (pHe) was reduced from 7.4 to 6.8 by increasing carbon dioxide (CO2) concentration from 4 to 15% in a HCO3-buffered solution or by NaOH titration in a Hepes-buffered solution. Both types of acidosis produced a slowing of the rate of terminal repolarization (i.e., period of repolarization starting at about -60 mV and ending at the maximum diastolic potential) with an attendant increase in action potential duration of 10--20 ms. This was accompanied by a reduction in the maximum diastolic potential of 2--8 mV. In contrast, if the same pH change was made by keeping CO2 concentration constant and lowering extracellular HCO3 from 23.7 to 6.0 mM, in addition to the slowing of terminal repolarization, the plateau was markedly prolonged resulting in an additional 50- to 80-ms increase in action potential duration. If pHe was held constant at 7.4 and HCO3 reduced from 23.7 mM to 0 (Hepes-buffered solution), the changes in repolarization were nearly identical to those seen in 6.0 mM HCO3 except that terminal repolarization was unchanged. This response was unaltered by doubling the concentration of Hepes. Reducing HCO3 to 12.0 mM produced changes in repolarization of about one-half the magnitude of those in 6.0 mM HCO3. These findings suggest that in Purkinje fibers, HCO3 either acts as a current that slows repolarization or modulates the ionic currents responsible for repolarization.


1994 ◽  
Vol 80 (6) ◽  
pp. 1360-1368 ◽  
Author(s):  
David F. Stowe ◽  
Juraj Sprung ◽  
Lawrence A. Turner ◽  
John P. Kampine ◽  
Zeljko J. Bosnjak

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