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Am J Physiol Heart Circ Physiol 276: H9-H18, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 1, H9-H18, January 1999

Positive force- and [Ca2+]i-frequency relationships in rat ventricular trabeculae at physiological frequencies

Joanne Layland and Jonathan C. Kentish

Department of Pharmacology, King's College London, St. Thomas's Campus, London SE1 7EH, United Kingdom

The isometric force-frequency relationship of isolated rat ventricular trabeculae (diameter <250 µm) was examined at 24, 30, and 37°C at stimulation frequencies (0.1-12 Hz) encompassing the physiological range. Some muscles were microinjected with fura PE3 to monitor the diastolic and systolic intracellular concentration of Ca2+ ([Ca2+]i). At a near-physiological external Ca2+ concentration ([Ca2+]o) of 1 mM, a positive force-frequency relationship was demonstrated at all temperatures. The force-frequency relationship became negative at high frequencies (e.g., >6 Hz at 30°C) at 1 mM [Ca2+]o or at low frequencies at 8 mM [Ca2+]o. The twitch and Ca2+ transient became shorter as stimulation frequency increased; these changes were related to changes in systolic, rather than diastolic, [Ca2+]i and were not blocked by inhibitors of Ca2+/calmodulin-dependent protein kinase II. The positive force-frequency relationship of rat trabeculae was caused by a frequency-dependent loading of the sarcoplasmic reticulum (SR) with Ca2+. We suggest that at high frequencies, or under conditions of Ca2+ overload, this loading saturates. Processes that tend to decrease SR Ca2+ release will then predominate, resulting in a negative force-frequency relationship.

fura PE3; calcium uptake by sarcoplasmic reticulum; calcium/calmodulin-dependent protein kinase


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