Modulation of delayed rectifier potassium current, iK, by isoprenaline in rabbit isolated pacemaker cells.
Permeabilized patch whole-cell voltage clamp methods were used to investigate the effects of isoprenaline (ISO) on total delayed rectifier potassium current, iK, in rabbit sino-atrial (SA) node pacemaker cells; total iK is composed of the rapidly activating iKr and the slowly activating iKs, but predominantly iKr in this species. ISO (20 nM) increased the amplitude of total iK and caused a negative shift of approximately 10 mV in the activation curve for iK, both in the absence and in the presence of 300 nM nisoldipine to block the L-type Ca2+ current, iCa,L. The same concentration (20 nM) of ISO increased the spontaneous pacemaker rate of SA node pacemaker cells by 16%. In addition to increasing the amplitude of iK, ISO (20-50 nM) also increased the rate of deactivation of this current. The stimulation of iK by ISO was reversed by 10 microM H-89, a selective protein kinase A inhibitor, but not by 200 nM bisindolymaleimide I, a selective protein kinase C inhibitor. It therefore appears that the mechanisms by which -adrenoceptor agonists increase pacemaking rate in sinoatrial node pacemaker cells include an increase in the rate of deactivation of iK in addition to the well-documented augmentation of iCa,L and the positive shift of the activation curve for the hyperpolarization-activated inward current, if. The observations are also consistent with a role for protein kinase A in the stimulation of iK by ISO in SA node cells.
Lei
M
M
University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. ming.lei@physiol.ox.ac.uk
Brown
H F
HF
Terrar
D A
DA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000465:Algorithms; D000818:Animals; D002469:Cell Separation; D051668:Delayed Rectifier Potassium Channels; D004594:Electrophysiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects*; D013268:Stimulation, Chemical; D013449:Sulfonamides
D000318:Adrenergic beta-Agonists; D051668:Delayed Rectifier Potassium Channels; D007546:Isoquinolines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; D007545:Isoproterenol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide