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This Article Full Text Full Text (PDF) All Versions of this Article: 585/2/579    most recent jphysiol.2007.141473v1 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 Google Scholar Google Scholar Articles by Dibb, K. M. Articles by Trafford, A. W. Search for Related Content PubMed PubMed Citation Articles by Dibb, K. M. Articles by Trafford, A. W. Related Collections Cardiovascular

¹ Unit of Cardiac Physiology, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK

The force–frequency response is an important physiological mechanism regulating cardiac output changes and is accompanied in vivo by β-adrenergic stimulation. We sought to determine the role of sarcoplasmic reticulum (SR) Ca²⁺ content and L-type current (I_Ca-L) in the frequency response of the systolic Ca²⁺ transient alone and during β-adrenergic stimulation. Experiments (on single rat ventricular myocytes) were designed to be as physiological as possible. Under current clamp stimulation SR Ca²⁺ content increased in line with stimulation frequency (1–8 Hz) but the systolic Ca²⁺ transient was maximal at 6 Hz. Under voltage clamp, increasing frequency decreased both systolic Ca²⁺ transient and I_Ca-L. Normalizing peak I_Ca-L by altering the test potential decreased the Ca²⁺ transient amplitude less than an equivalent reduction achieved through changes in frequency. This suggests that, in addition to SR Ca²⁺ content and I_Ca-L, another factor, possibly refractoriness of Ca²⁺ release from the SR contributes. Under current clamp, β-adrenergic stimulation (isoprenaline, 30 nM) increased both the Ca²⁺ transient and the SR Ca²⁺ content and removed the dependence of both on frequency. In voltage clamp experiments, β-adrenergic stimulation still increased SR Ca²⁺ content yet there was an inverse relation between frequency and Ca²⁺ transient amplitude and I_Ca-L. Diastolic [Ca²⁺]_i increased with stimulation frequency and this contributed substantially (69.3 ± 6% at 8 Hz) to the total Ca²⁺ efflux from the cell. We conclude that Ca²⁺ flux balance is maintained by the combination of increased efflux due to elevated diastolic [Ca²⁺]_i and a decrease of influx on I_Ca-L on each pulse.

(Received 25 July 2007; accepted after revision 5 October 2007; first published online 11 October 2007)
Corresponding author K. M. Dibb: Unit of Cardiac Physiology, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK. Email: katharine.dibb{at}manchester.ac.uk