Article

KV2 channels oppose myogenic constriction of rat cerebral arteries

Dept. of Physics and Biophysics, Univ. of Washington, PO Box 357290, Seattle, WA 98195, USA.
AJP Cell Physiology (Impact Factor: 3.78). 09/2006; 291(2):C348-56. DOI: 10.1152/ajpcell.00086.2006
Source: PubMed

ABSTRACT

By hyperpolarizing arterial smooth muscle, voltage-gated, Ca2+-independent K+ (Kv) channels decrease calcium influx and thus oppose constriction. However, the molecular nature of the Kv channels function in arterial smooth muscle remains controversial. Recent investigations have emphasized a predominant role of Kv1 channels in regulating arterial tone. In this study, we tested the hypothesis Kv2 channels may also significantly regulate tone of rat cerebral arteries. We found that Kv2.1 transcript and protein are present in cerebral arterial smooth muscle. In addition, our analysis indicates that a substantial component (approximately 50%) of the voltage dependencies and kinetics of Kv currents in voltage-clamped cerebral arterial myocytes is consistent with Kv2 channels. Accordingly, we found that stromatoxin, a specific inhibitor of Kv2 channels, significantly decreased Kv currents in these cells. Furthermore, stromatoxin enhanced myogenic constriction of pressurized arterial segments. We also found that during angiotensin II-induced hypertension, Kv2 channel function was reduced in isolated myocytes and in intact arteries. This suggests that impaired Kv2 channel activity may contribute to arterial dysfunction during hypertension. On the basis of these novel observations, we propose a new model of Kv channel function in arterial smooth muscle in which Kv2 channels (in combination with Kv1 channels) contribute to membrane hyperpolarization and thus oppose constriction.

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Available from: Gregory C Amberg, Nov 21, 2015
    • "Under physiological conditions, Kv channels contribute to the feedback regulation of the myogenic response in resistance VSMCs (Amberg and Santana, 2006;Chen et al., 2006). The myogenic response consists of small depolarizations induced by increases in blood pressure in the resistance vessels. "
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    • "subunits could be identified [7] [11] [12]. In situ hybridization revealed the presence of different BK channel splice variants (X1 +24 , X2 +92 , SS2 +174 and SS4 +81 ) in combination with β1, β2, and β4 subunits in rat cerebral arteries [13]. "
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    ABSTRACT: Healthy cerebrovascular myocytes express members of several different ion channel families which regulate resting membrane potential, vascular diameter, and vascular tone and are involved in cerebral autoregulation. In animal models, in response to subarachnoid blood, a dynamic transition of ion channel expression and function is initiated, with acute and long-term effects differing from each other. Initial hypoperfusion after exposure of cerebral vessels to oxyhemoglobin correlates with a suppression of voltage-gated potassium channel activity, whereas delayed cerebral vasospasm involves changes in other potassium channel and voltage-gated calcium channels expression and function. Furthermore, expression patterns and function of ion channels appear to differ between main and small peripheral vessels, which may be key in understanding mechanisms behind subarachnoid hemorrhage-induced vasospasm. Here, changes in calcium and potassium channel expression and function in animal models of subarachnoid hemorrhage and transient global ischemia are systematically reviewed and their clinical significance discussed.
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    • "Within hippocampal neurons Kv2.1 regulates the action potential waveform, especially during high-frequency stimulation (Du et al., 2000). In pulmonary vascular smooth muscle Kv2.1 represents a hypoxia-sensitive channel that regulates the membrane potential and thus smooth muscle contraction (Patel et al., 1997; Hulme et al., 1999), and in cerebral artery smooth muscle Kv2.1 regulates myogenic constriction (Amberg and Santana, 2006). In the myocardium Kv2.1 generates the "
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