Kv1.3 channels facilitate the connection between metabolism and blood flow in the heart.

Kv1.3 channels facilitate the connection between metabolism and blood flow in the heart.

Ohanyan Vahagn; Yin Liya; Bardakjian Raffi; Kolz Christopher; Enrick Molly; Hakobyan Tatevik; Luli Jordan; Graham Kathleen; Khayata Mohamed; Logan Suzanna; Kmetz John; Chilian William M

Microcirculation (New York, N.Y. : 1994)

2017

2017-05

The connection between metabolism and flow in the heart, metabolic dilation, is essential for cardiac function. We recently found redox-sensitive Kv1.5 channels play a role in coronary metabolic dilation; however, more than one ion channel likely plays a role in this process as animals null for these channels still showed limited coronary metabolic dilation. Accordingly, we examined the role of another Kv1 family channel, the energetically linked Kv1.3 channel, in coronary metabolic dilation. We measured myocardial blood flow (contrast echocardiography) during norepinephrine-induced increases in cardiac work (heart rate x mean arterial pressure) in WT, WT mice given correolide (preferential Kv1.3 antagonist), and Kv1.3-null mice (Kv1.3(-/-) ). We also measured relaxation of isolated small arteries mounted in a myograph. During increased cardiac work, myocardial blood flow was attenuated in Kv1.3(-/-) and in correolide-treated mice. In isolated vessels from Kv1.3(-/-) mice, relaxation to H2 O2 was impaired (vs WT), but responses to adenosine and acetylcholine were equivalent to WT. Correolide reduced dilation to adenosine and acetylcholine in WT and Kv1.3(-/-) , but had no effect on H2 O2 -dependent dilation in vessels from Kv1.3(-/-) mice. We conclude that Kv1.3 channels participate in the connection between myocardial blood flow and cardiac metabolism.

*contrast echocardiography; *coronary blood flow; *Coronary Circulation/drug effects; *coronary microcirculation; *Kv 1.3 channels; Animals; Kv1.3 Potassium Channel/*physiology; Mice; Myocardium/*metabolism; Potassium Channel Blockers/pharmacology; Regional Blood Flow/drug effects; Triterpenes/pharmacology; Vasodilation/drug effects

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