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Modulation of delayed rectifier potassium current, iK, by isoprenaline in rabbit isolated pacemaker cells
1University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. ming.lei@physiol.ox.ac.uk
Experimental Physiology
|February 9, 2000
Summary
Isoprenaline (ISO) increases heart rate by affecting potassium currents in sinoatrial (SA) node pacemaker cells. This study shows ISO enhances the delayed rectifier potassium current (iK) and its deactivation rate, mediated by protein kinase A.
Area of Science:
- Cardiovascular Physiology
- Electrophysiology
- Molecular Cardiology
Background:
- The sinoatrial (SA) node controls heart rate through complex ion channel activity.
- Isoprenaline (ISO) is known to increase heart rate, but the precise mechanisms involving potassium currents are not fully elucidated.
Purpose of the Study:
- To investigate the effects of ISO on the total delayed rectifier potassium current (iK) in rabbit SA node pacemaker cells.
- To determine the role of protein kinase A (PKA) in ISO-mediated stimulation of iK.
Main Methods:
- Permeabilized patch whole-cell voltage clamp.
- Electrophysiological recordings in rabbit SA node pacemaker cells.
- Pharmacological manipulation using ISO, nisoldipine, H-89, and bisindolylmaleimide I.
Main Results:
- ISO (20 nM) significantly increased the amplitude of total iK and shifted its activation curve negatively.
- ISO also increased the spontaneous pacemaker rate of SA node cells by 16%.
- ISO accelerated the deactivation rate of iK, an effect reversed by PKA inhibition (H-89) but not PKC inhibition.
Conclusions:
- ISO enhances iK amplitude and deactivation rate in SA node cells, contributing to increased pacemaking.
- The findings support a role for PKA in mediating ISO's effects on iK.
- These mechanisms, alongside augmentation of L-type calcium current (iCa,L) and the hyperpolarization-activated inward current (if), explain ISO's chronotropic effect.