title: Contribution of frequency-augmented inward Ca2+ current to myocardial contractility.
abstract: The sarcoplasmic reticular Ca2+ pump (SERCA) is thought to be the primary determinant of heart rate-dependent increases in myocardial contractile [Ca2+]i and force (force-frequency relationship (FFR)), an important mechanism to increase cardiac output. This report demonstrates a rate-dependent role for inward Ca2+ current (ICa) in the human and rat FFR. Human action potential plateau height increased linearly with contractility when heart rate increased in vivo, as measured by monophasic action potential catheter and echocardiography. Rat rate-dependent developed force and cytosolic [Ca2+]i transients were quantified in isolated left ventricular papillary muscles, and ICa and action potential duration in cardiomyocytes. ICa and SERCA measurements better reflected [Ca2+]i and force transients than SERCA activity alone. These data support a direct and (or) indirect contribution to myocardial contractility by ICa at heart rates from approximately 1 to 3-4 Hz (60 to 180-240 bpm) in tandem with SERCA to sustain the typical 'bell shape' of the FFR across species.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Parilak
authors.forename: David G
authors.initials: DG
authors.lastname: Taylor
authors.forename: Yejia
authors.initials: Y
authors.lastname: Song
authors.forename: Thomas
authors.initials: T
authors.lastname: Burkart
authors.forename: John C
authors.initials: JC
authors.lastname: Shryock
authors.forename: Anne B
authors.initials: AB
authors.lastname: Curtis
authors.forename: Harm J
authors.initials: HJ
authors.lastname: Knot
mesh_terms: D000200:Action Potentials; D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D051381:Rats; D011921:Rats, Inbred WKY; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology
chemical_list: D015220:Calcium Channels; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium