title: Ca2+ cycling in heart cells from ground squirrels: adaptive strategies for intracellular Ca2+ homeostasis.
abstract: Heart tissues from hibernating mammals, such as ground squirrels, are able to endure hypothermia, hypoxia and other extreme insulting factors that are fatal for human and nonhibernating mammals. This study was designed to understand adaptive mechanisms involved in intracellular Ca(2+) homeostasis in cardiomyocytes from the mammalian hibernator, ground squirrel, compared to rat. Electrophysiological and confocal imaging experiments showed that the voltage-dependence of L-type Ca(2+) current (I(Ca)) was shifted to higher potentials in ventricular myocytes from ground squirrels vs. rats. The elevated threshold of I(Ca) did not compromise the Ca(2+)-induced Ca(2+) release, because a higher depolarization rate and a longer duration of action potential compensated the voltage shift of I(Ca). Both the caffeine-sensitive and caffeine-resistant components of cytosolic Ca(2+) removal were more rapid in ground squirrels. Ca(2+) sparks in ground squirrels exhibited larger amplitude/size and much lower frequency than in rats. Due to the high I(Ca) threshold, low SR Ca(2+) leak and rapid cytosolic Ca(2+) clearance, heart cells from ground squirrels exhibited better capability in maintaining intracellular Ca(2+) homeostasis than those from rats and other nonhibernating mammals. These findings not only reveal adaptive mechanisms of hibernation, but also provide novel strategies against Ca(2+) overload-related heart diseases.
authors.affiliation: State Key Lab of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Guang-Qin
authors.initials: GQ
authors.lastname: Zhang
authors.forename: Zai-Ling
authors.initials: ZL
authors.lastname: Bai
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Hu
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Bai
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chai
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Hao
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D006706:Homeostasis; D008564:Membrane Potentials / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D012589:Sciuridae; D013696:Temperature
chemical_list: D002118:Calcium