Positive force- and [Ca2+]i-frequency relationships in rat ventricular trabeculae at physiological frequencies.
The isometric force-frequency relationship of isolated rat ventricular trabeculae (diameter <250 micrometer) was examined at 24, 30, and 37 degreesC 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 degreesC) 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.
Layland
J
J
Department of Pharmacology, King's College London, St. Thomas's Campus, London SE1 7EH, United Kingdom.
Kentish
J C
JC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013696:Temperature; D013997:Time Factors; D016276:Ventricular Function / Q000502:physiology*
D004791:Enzyme Inhibitors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium