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The Role of Potassium Voltage Gated Kv 1.2 Channels in Coronary Metabolic Dilatation
Author(s) -
Ohanyan Vahagn A,
Bratz Ian N,
Kolz Christopher L,
Guarini Giacinta,
Luther Daniel J.,
Yin Liya,
Pung Yuh Fen,
Chilian William M.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1023.15
Subject(s) - medicine , blood flow , cardiology , chemistry , cardiac function curve , potassium channel , coronary circulation , heart rate , cardiac output , endocrinology , blood pressure , heart failure
Kv channels are important for function of vascular smooth muscle. Coronary arterioles express members of the Kv1 channel family: Kv1.2, 1.3, and 1.5. These channels are redox and oxygen regulated which makes them possible transducers of metabolic dilation in the heart. Total knockout of Kv1.2 channels is lethal, which may reflect their importance coupling metabolism to flow. Thus, we hypothesized that Kv1.2 channels are critical for coronary metabolic dilation. To investigate this, we studied the relationship between cardiac work and myocardial blood flow in genetically modified mice heterozygous null for the Kv 1.2 channel (Kv 1.2 +/− ) and their wild type controls (Kv1.2 +/+ ). Cardiac work (stroke volume [SV] X heart rate [HR] X mean arterial pressure [MAP]) was measured during infusion of norepinephrine (NE 0.5, 1.0, 2.5 and 5.0 μg/kg/min, iv.). MAP and HR were measured using a Millar transducer, SV via echocardiography and MBF using contrast echocardiography. At baseline MBF was equivalent in Kv 1.2 +/− mice and WT. At high levels of cardiac work produced by NE, the increase in MBF was 42%±6 less in Kv 1.2 +/− mice compared to WT (P<0.05). Interestingly at high doses of NE, cardiac function deteriorated in the Kv 1.2 +/− mice suggesting that flow was inadequate to match the metabolic needs of the myocardium. Based on our data, we conclude that Kv 1.2 channels play a key role in coupling myocardial metabolism to MBF.