title: Altered Ca2+ handling and myofilament desensitization underlie cardiomyocyte performance in normothermic and hyperthermic heat-acclimated rat hearts.
abstract: Heat acclimation (AC) improves cardiac mechanical and metabolic performance. Using cardiomyocytes and isolated hearts from 30-day and 2-day acclimated rats (AC and AC-2d, 34 degrees C), we characterized cellular contractile mechanisms under normothermic (37 degrees C) and hyperthermic (39-42 degrees C) conditions. To determine contractile responses, Ca2+ transients (Ca2+ T), sarcoplasmic reticulum (SR) Ca2+ pool size (fura-2/indo-1 fluorescence), force generation [amplitude systolic motion (ASM)], L-type Ca2+ channels [dihydropyridine receptor (DHPR)], ryanodine receptors (RyRs), and total (PLBt) and phosphorylated phospholamban [serine phosphorylated (PLBs) and theonine phosphorylated (PLBtr)] proteins and transcripts were measured (Western blot, RT-PCR). Cardiac mechanical performance was measured using a Langendorff system. We demonstrated that AC and AC-2d increased Ca2+ T amplitude (148% and 147%, respectively) and twitch force (180% and 130%, respectively) and desensitized myofilaments, as indicated by a rightward shift in the ASM-Ca2+ relationships, despite no change in SR Ca2+ pool size. Hence, generation of higher Ca2+ T underlies greater force development in AC and AC-2d myocytes. In isolated hearts, ryanodine administration eliminated differences between AC and control (C) hearts, implying an important role for RyRs in that acclimation phase. Increased expression of DHPR and RyRs, and decreased PLBs/PLBt in AC hearts only, suggest that different pathways increase force generation in the AC-2d vs. AC myocytes. At basal beating rates, hyperthermia (39-41 degrees C) enhanced pressure generation in AC hearts. C hearts failed to restitute pressure beyond 39 degrees C. Increased beating frequency produced negative inotropic response. In C cardiomyocytes, hyperthermia elevated basal cytosolic Ca2+ and tension, Ca2+ T, and ASM. AC myocytes enhanced Ca2+ T but showed myofilament desensitization, suggesting its involvement in cardiac protection against hyperthermia. Collectively, both Ca2+ turnover and myofilament responsiveness are important adaptive acclimatory targets during normothermic and hyperthermic conditions.
authors: Laboratory of Environmental Physiology, Faculty of Dental Medicine, Hadassah Medical Center, The Hebrew University, Jerusalem 91120, Israel.
authors: Omer
authors: O
authors: Cohen
authors: Hifa
authors: H
authors: Kanana
authors: Ronen
authors: R
authors: Zoizner
authors: Chaya
authors: C
authors: Gross
authors: Uri
authors: U
authors: Meiri
authors: Michael D
authors: MD
authors: Stern
authors: Gary
authors: G
authors: Gerstenblith
authors: Michal
authors: M
authors: Horowitz
mesh_terms: D000064:Acclimatization; D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005334:Fever / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate; D018882:Heat Stress Disorders / Q000378:metabolism / Q000503:physiopathology*; D006358:Hot Temperature; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D017725:Ventricular Pressure; D000099211:Phospholamban
chemical_list: D002118:Calcium; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D012433:Ryanodine; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C506948:Atp2a2 protein, rat