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This Article Full Text Full Text (PDF) Supplmental Data All Versions of this Article: 574/1/183    most recent jphysiol.2006.105015v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rocchetti, M. Articles by Zaza, A. Search for Related Content PubMed PubMed Citation Articles by Rocchetti, M. Articles by Zaza, A. Related Collections Cellular

¹ Dipartimento di Biotecnologie e Bioscienze, Università degli Studi Milano-Bicocca, Milano, Italy

ß-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 µM Iso (I_Iso); (2) the L-type Ca²⁺ 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 (APD₉₀) 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 APD₉₀. 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 APD₉₀–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 APD₉₀ was CL dependent, and negligible during tachycardia; and (3) during sympathetic activation, repolarization stability may involve matched modulation of sinus rate and repolarizing currents.

(Received 9 January 2005; accepted after revision 13 February 2006; first published online 16 February 2006)
Corresponding author A. Zaza: Università di Milano-Bicocca, Dipartimento di Biotecnologie e Bioscienze, Piazza della Scienza 2, room U3-3013, 20126 Milano, Italy. Email: antonio.zaza{at}unimib.it

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