Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences.
Males and females show distinct differences in action potential waveform, ion channel expression patterns, and ECG characteristics. However, it is not known how sex-based differences in Ca2+ cycling might contribute to these differences in electrophysiological activity. The goal of this study was to investigate the differences in cellular Ca2+ transients in males and females and to examine how these might contribute to electrophysiological function. Ca2+ transients were measured in individual myocytes within microscopic regions of the fluo-4 AM-loaded left ventricular epicardium of intact rat heart of both sexes (3 to 5 mo old). Pacing protocols were used to measure transient characteristics at a basic cycle length of 500 ms and during 10-s trains of rapid pacing delivered to the left ventricular apex. Ca2+ transients were smaller in magnitude and longer in duration in females than in males. More importantly, the variability in Ca2+ transient characteristics between myocytes in a microscopic recording site (heterogeneity index) was greater for females than males for characteristics related to transient duration. The rate sensitivity of Ca2+ alternans development in individual myocytes was greater in females than in males, but there was also a greater heterogeneity in cellular responses to the rate dependence of alternans development in females. The longer Ca2+ transients in females were also associated with slower restitution, which was likely to be responsible for the development of Ca2+ and repolarization alternans at slower heart rates. These results demonstrate that there are distinct differences in cellular Ca2+ cycling in male and female rat hearts. Not only is there slower reuptake of Ca2+ in female rats, but there is greater local variability in Ca2+ cycling at the microscopic level. These sex-based differences in Ca2+ cycling could contribute to differences in ECG morphology and in arrhythmia sensitivity in males and females.
Wasserstrom
J Andrew
JA
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ja-wasserstrom@northwestern.edu
Kapur
Sunil
S
Jones
Sabrina
S
Faruque
Tania
T
Sharma
Rohan
R
Kelly
James E
JE
Pappas
Amanda
A
Ho
Wilson
W
Kadish
Alan H
AH
Aistrup
Gary L
GL
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism; D020013:Calcium Signaling; D002304:Cardiac Pacing, Artificial; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010496:Pericardium / Q000378:metabolism; D051381:Rats; D012737:Sex Factors
Circulation. 2002 Jul 23;106(4):497-503
12135952
Am J Physiol. 1997 Nov;273(5):H2161-9
9374749
Basic Res Cardiol. 2004 May;99(3):183-92
15088103
Circ Res. 1988 Mar;62(3):563-71
2449297
Cardiovasc Res. 2002 Feb 15;53(3):740-51
11861044
J Physiol. 2006 Jul 15;574(Pt 2):519-33
16709642
Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H570-80
16501015
Prog Biophys Mol Biol. 2007 Jul;94(3):265-319
15979693
Br Heart J. 1982 Sep;48(3):213-6
7104111
Circ Res. 2006 Sep 29;99(7):e65-73
16960102
Circ Res. 2003 Apr 4;92(6):668-75
12600876
Circulation. 2001 Oct 23;104(17):2082-7
11673350
J Physiol. 1998 Sep 1;511 ( Pt 2):533-48
9706029
Cardiovasc Res. 2003 Jan;57(1):28-36
12504811
Circ Res. 1988 Aug;63(2):286-305
3396153
J Mol Cell Cardiol. 2005 Sep;39(3):419-28
16026799
Am J Physiol. 1971 Jun;220(6):1708-16
5087820
Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3506-16
17906109
Circ Res. 2004 Mar 19;94(5):650-6
14752033
J Membr Biol. 1996 Feb;149(3):169-77
8801349
Proc Biol Sci. 1994 Feb 22;255(1343):125-32
8165225
Circ Res. 2004 Mar 19;94(5):570-2
15031268
Life Sci. 2005 Apr 22;76(23):2735-49
15792839
Am J Physiol Heart Circ Physiol. 2002 May;282(5):H1889-97
11959656