Acid-sensing ion channel 3, but not capsaicin receptor TRPV1, plays a protective role in isoproterenol-induced myocardial ischemia in mice.
BACKGROUND
Cardiac angina is the hallmark of myocardial ischemia, but the role of the cardiac sensory nerve has received relatively little attention. Recently, both acid-sensing ion channel 3 (ASIC3) and capsaicin receptor (TRPV1) have been suggested as important mediators in sensing cardiac ischemia. However, studies comparing the physiological roles of ASIC3 and TRPV1 in the neuronal-cardiac sensing circuits in vivo are lacking.


RESULTS
Isoproterenol (1.5 mg/kg, intraperitoneally) was used to induce transient cardiac ischemia in Asic3(+/+) and Asic3(-/-) mice and a radio-telemetry system was used for electrocardiography with mice in a conscious state. Isoproterenol-induced cardiac ischemia was first demonstrated with ST-segment depression and further confirmed by hypoxia-mediated chemical reactions in cardiac tissue. Mice lacking Asic3 showed prolonged duration of ST-segment depression compared with Asic3(+/+) mice (44.3 ± 3.1 vs. 31.7 ± 2.9 min; P < 0.05). Although ischemia was transient, severe cardiac fibrosis was found in Asic3(-/-) but not in Asic3(+/+) mice littermates. In contrast, isoproterenol-injected Trpv1(+/+) and Trpv1(-/-) mice showed no difference in duration of ST-segment depression and, surprisingly, deletion of Trpv1 did not aggravate cardiac fibrosis.


CONCLUSIONS
An isoproterenol-induced cardiac ischemia model mimicking clinical conditions of early cardiac angina was used to demonstrate that ASIC3 but not TRPV1 plays a protective role in sensing cardiac ischemia.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Ching-Feng
CF
Cheng
I-Lun
IL
Chen
Mei-Hsin
MH
Cheng
Wei-Shiung
WS
Lian
Chao-Chieh
CC
Lin
Terry B J
TB
Kuo
Chih-Cheng
CC
Chen
D062565:Acid Sensing Ion Channels; D000818:Animals; D004195:Disease Models, Animal; D015716:Electrocardiography, Ambulatory; D005355:Fibrosis; D007545:Isoproterenol; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013686:Telemetry; D013997:Time Factors
C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D007545:Isoproterenol