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This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/H1623    most recent 01245.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Shutt, R. H. Articles by Howlett, S. E. Search for Related Content PubMed PubMed Citation Articles by Shutt, R. H. Articles by Howlett, S. E.

Increases in diastolic [Ca²⁺] can contribute to positive inotropy in guinea pig ventricular myocytes in the absence of changes in amplitudes of Ca²⁺ transients

Robin H. Shutt, Gregory R. Ferrier, and Susan E. Howlett

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada

Submitted 25 November 2005 ; accepted in final form 9 May 2006

Increases in contraction amplitude following rest or in elevated extracellular Ca²⁺ concentration ([Ca²⁺]) have been attributed to increased sarcoplasmic reticulum (SR) Ca²⁺ stores and/or increased trigger Ca²⁺. However, either manipulation also may elevate diastolic [Ca²⁺]. The objective of this study was to determine whether elevation of diastolic [Ca²⁺] could contribute to positive inotropy in isolated ventricular myocytes. Voltage-clamp experiments were conducted with high-resistance microelectrodes in isolated myocytes at 37°C. Intracellular free [Ca²⁺] was measured with fura-2, and cell shortening was measured with an edge detector. SR Ca²⁺ stores were assessed with 10 mM caffeine (0 mM Na⁺, 0 mM Ca²⁺). Following a period of rest, cells were activated with trains of pulses, which generated contractions of increasing amplitude, called positive staircases. Positive staircases were accompanied by increasing diastolic [Ca²⁺] but no change in Ca²⁺ transient amplitudes. When extracellular [Ca²⁺] was elevated from 2.0 to 5.0 mM, resting intracellular [Ca²⁺] increased and resting cell length decreased. Amplitudes of contractions and L-type Ca²⁺ current increased in elevated extracellular [Ca²⁺], although SR Ca²⁺ stores, assessed by rapid application of caffeine, did not increase. Although Ca²⁺ transient amplitude did not increase in 5.0 mM extracellular [Ca²⁺], diastolic [Ca²⁺] continued to increase with increasing extracellular [Ca²⁺]. These data suggest that increased diastolic [Ca²⁺] contributes to positive inotropy following rest or with increasing extracellular [Ca²⁺] in guinea pig ventricular myocytes.

excitation-contraction coupling; fura-2 fluorescence; extracellular Ca²⁺ concentration; positive staircases

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				R. H. Shutt and S. E. Howlett Hypothermia increases the gain of excitation-contraction coupling in guinea pig ventricular myocytes Am J Physiol Cell Physiol, September 1, 2008; 295(3): C692 - C700. [Abstract] [Full Text] [PDF]