Acid-sensing ion channel 3, but not capsaicin receptor TRPV1, plays a protective role in isoproterenol-induced myocardial ischemia in mice.

Abstract

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.

METHODS AND 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.

• Authors: Ching-Feng Cheng, I-Lun Chen, Mei-Hsin Cheng, Wei-Shiung Lian, Chao-Chieh Lin, Terry B J Kuo, Chih-Cheng Chen
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 75 Issue 1 Pg. 174-8 ( 2011) ISSN: 1347-4820 [Electronic] Japan
• PMID: 21127383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ASIC3 protein, mouse
• Acid Sensing Ion Channels
• Sodium Channels
• TRPV Cation Channels
• TRPV1 protein, mouse
• Isoproterenol

Topics

• Acid Sensing Ion Channels
• Animals
• Disease Models, Animal
• Electrocardiography, Ambulatory
• Fibrosis
• Isoproterenol
• Male
• Mice
• Mice, 129 Strain
• Mice, Knockout
• Mice, Transgenic
• Myocardial Ischemia (chemically induced, metabolism, pathology, prevention & control)
• Myocardium (metabolism, pathology)
• Sodium Channels (deficiency, genetics, metabolism)
• TRPV Cation Channels (deficiency, genetics, metabolism)
• Telemetry
• Time Factors