Quantification of the rat left ventricle force and Ca2+ -frequency relationships: similarities to dog and human.
OBJECTIVE
To measure and quantify the force-frequency (FFR) and Ca(2+)-frequency (CaFR) relationships in isolated rat left ventricular (LV) muscle at physiological heart rates and compare the obtained FFR to that measured in larger mammalian muscle from dog and human using the same experimental protocol.


METHODS
Rat papillary muscle was isolated from the LV of adult male Sprague-Dawley rats, and dog and human muscles were from free-wall LV biopsies, loaded with the Ca(2+) indicator Fura-2, allowed to recover from isolation trauma and then subjected to direct electrical stimulation while measuring force production and intracellular Ca(2+) transients.


RESULTS
We obtained a positive FFR between 1 and 4 Hz that is qualitatively similar to that found in isolated LV epicardial muscle strips from dogs and humans with normal LV function. The FFR reflects the cytosolic Ca(2+) transients in amplitude. Isoproterenol yielded an enhancement in force, but flattening of the FFR, whereas cyclopiazonic acid caused depression of FFR amplitude without changing frequency-dependent shape.


CONCLUSIONS
We describe an experimental protocol that consistently yields positive FFRs in rat, dog and human LV muscle at stimulation rates between 1 and 4 Hz, without significant qualitative differences. We attribute previously observed negative FFR in rat muscle to an increase in SERCA activity early after excision and preparation of the muscle strips.
Taylor
David G
DG
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA.
Parilak
Leonard D
LD
LeWinter
Martin M
MM
Knot
Harm J
HJ
D000368:Aged; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D007211:Indoles; D007545:Isoproterenol; D002118:Calcium; C000543:cyclopiazonic acid