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Rate dependency of β‐adrenergic modulation of repolarizing currents in the guinea‐pig ventricle
Author(s) -
Rocchetti M.,
Freli V.,
Perego V.,
Altomare C.,
Mostacciuolo G.,
Zaza A.
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.105015
Subject(s) - isoprenaline , repolarization , chemistry , medicine , ventricle , guinea pig , endocrinology , patch clamp , cardiology , biophysics , electrophysiology , stimulation , biology
β‐Adrenergic stimulation modulates ventricular currents and sinus cycle length (CL). We investigated how changes in CL affect the current induced by isoprenaline (Iso) during the action potential (AP) of guinea‐pig ventricular myocytes. Action‐potential clamp was applied at CLs of 250 and 1000 ms to measure: (1) the net current induced by 0.1 μ m Iso ( I Iso ); (2) the L‐type Ca 2+ current I CaL and slow delayed rectifier current I Ks components of I Iso ( I IsoCa and I IsoK ), identified as the Iso‐induced current sensitive to nifedipine and HMR1556, respectively; and (3) I Iso persisting after inhibition of both I Ca and I Ks ( I isoR ). The pause dependency of I Ks and its modulation were evaluated in voltage‐clamp experiments. The rate dependency of the duration of the action potential at 90% repolarization (APD 90 ) and its modulation by isoprenaline were tested in current‐clamp experiments. At a CL of 250 ms I Iso was inward during initial repolarization and reversed at 59% of APD 90 . At a CL of 1000 ms I Iso became mostly inward in all cells. Switching to shorter CL did not change I IsoCa and I IsoK amplitudes, but moved their peak amplitudes to earlier repolarization; I IsoR was independent of CL. Acceleration of I IsoK at shorter CL was based on faster pause dependency of I Ks activation rate. The ‘restitution’ of activation rates was modulated by isoprenaline. The APD 90 –CL relation was rotated anticlockwise by isoprenaline and crossed the control curve at a CL of 150 ms (400 beats min −1 ). We conclude that: (1) isoprenaline induced markedly different current profiles according to pacing rate, involving CL‐dependent I Ca and I Ks modulation; (2) the effect of isoprenaline on APD 90 was CL dependent, and negligible during tachycardia; and (3) during sympathetic activation, repolarization stability may involve matched modulation of sinus rate and repolarizing currents.