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(Circulation Research. 2005;96:e58.)
© 2005 American Heart Association, Inc.

Letter to the Editor

Regulation of Arterial Tone by K_V1 Potassium Channels

David J. Beech, Alex Cheong

School of Biomedical Sciences, University of Leeds, UK

Nancy J. Rusch

Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Little Rock

To the Editor:

We have read with interest the recent article published by Circulation Research entitled "Heteromultimeric Kv1 Channels Contribute to Myogenic Control of Arterial Diameter."¹ The study adds to an expanding body of evidence suggesting pivotal roles of the voltage-gated potassium channels (K_V channels) in vascular smooth muscle cells as regulators of arterial tone. Nevertheless, we feel it is necessary to point out some issues relating to representation of the literature by Plane et al.

A general sentiment conveyed by Plane et al is "This study indicates for the first time the importance of K_DR [delayed rectifier potassium] channels composed of K_V1 subunits to normal function of arterial resistance vessels via controlling their role in myogenic reactivity." However, although appropriate references are cited, it is not made apparent to the reader that this concept has been documented previously. For example, Cheong et al² showed that murine pial arterioles express K_V1 proteins in the smooth muscle cells and that the recombinant toxins agitoxin-2 and margatoxin (highly-specific K_V1 blockers) cause vasoconstriction. Also, K_V1 proteins were shown in smooth muscle cells of rabbit pial arterioles, and correolide, a K_V1-specific blocker (also central to the work of Plane et al), caused vasoconstriction.³ This study included recording of the K_DR potassium current, showing its block by correolide, and demonstrating specificity of correolide by heterologous expression studies. Finally, Albarwani et al⁴ found that rat small cerebral arteries express K_V1 proteins in the smooth muscle cells and that correolide inhibits the K_DR currents. In this preparation, which exhibits a high level of myogenic tone, block of K_V1 channels by correolide depolarized and constricted the pressurized arteries.

Plane et al also do not discuss a potential discrepancy between their finding that mRNA encoding K_V1 channels decreases with progression along the rat mesenteric arterial tree and findings supporting the opposite pattern of increased expression of K_V1 channels from aorta to mesenteric arteries of the rat or mouse.^5,6

Additionally, there are numerous errors in the description of the work of other laboratories. A partial list includes:

1. Page 1 to 2: "Expression of these transcripts ... was reported ... including K_V1.1 and K_V1.6.^{6,7,15,18–23}" References 7, 21, and 22 do not provide any data on transcripts. Reference 7 includes only patch-clamp data.
   
2. Page 3: "K_V1.1 and/or K_V1.6 expression was reported for cerebral and mesenteric arteries.^{6,7,15,19,24,25}" Reference 7 is a patch-clamp study without reference to detection of specific subunits. Reference 19 reports that transcripts for K_V1.1 and K_V1.6 could not be detected in rat mesenteric artery. References 24 and 25 characterize correolide effects in lymphocytes and HEK-293 cells, not blood vessels.
   
3. Page 4: "Similarly, a lack of K_V1.1 protein expression by rat cerebral arterial myocytes was also evident using this antibody, contrary to previous reports.^15,22" Reference 15 detected only K_V1.2 and K_V1.5 protein. Reference 22 detected only K_V1.2, K_V1.5 and K_V1.6 proteins, which is the same as concluded by Plane et al.
   
4. Page 7: "Evidence for contribution of K_V1.1 ... was not obtained ... contrary to studies of small arteries and arterioles.^{6,7,15,22,23,31}" Reference 7 is a patch-clamp study and there is no comment on K_V1.1 expression. References 15, 22, and 23 all conclude that K_V1.1 is not a protein of smooth muscle cells in small arteries and arterioles. In general, the authors present a misleading perspective of K_V1.1 studies in blood vessels.
   
5. Page 8: "Inhibition of K_DR by correolide was previously shown to elicit depolarisation and constriction of cerebral arteries and/or arterioles.^5,15,24 Reference 5 did not use correolide, and reference 24 did not use blood vessels.
   

We would like to stress that this letter is not a comment on the data in Plane et al. In fact, the findings of this article support previous conclusions that heteromultimeric K_V1 channels are expressed in vascular smooth muscle cells and regulate arterial tone. Our intention is, instead, to set Plane et al in perspective and take steps toward clarifying current knowledge for those who might read Plane et al as a primary source of information on this emerging and important aspect of vascular biology.

References

1. Plane F, Johnson R, Kerr P, Wiehler W, Thorneloe K, Ishii K, Chen T, Cole W. Heteromultimeric K_V1 channels contribute to myogenic control of arterial diameter. Circ Res. 2005; 96: 216–224[Abstract/Free Full Text]
2. Cheong A, Dedman AM, Xu SZ, Beech DJ. K_V1 channels in murine arterioles: differential cellular expression and regulation of diameter. Am J Physiol Heart Circ Physiol. 2001; 281: H1057–H1065.[Abstract/Free Full Text]
3. Cheong A, Dedman AM, Beech DJ. Expression and function of native potassium channel K_V1 subunits in terminal arterioles of rabbit. J Physiol. 2001; 534: 691–700.[Abstract/Free Full Text]
4. Albarwani S, Nemetz LT, Madden JA, Tobin AA, England SK, Pratt PF, Rusch NJ. Voltage-gated K⁺ channels in rat small cerebral arteries: molecular identity of the functional channels. J Physiol. 2003; 551: 751–763.[Abstract/Free Full Text]
5. Cox RH, Lozinskaya I, Dietz NJ. Differences in K⁺ current components in mesenteric artery myocytes from WKY and SHR. Am J Hypertens. 2001; 14: 897–907.[CrossRef][Medline] [Order article via Infotrieve]
6. Fountain SJ, Cheong A, Flemming R, Mair L, Sivaprasadarao A, Beech DJ. Functional up-regulation of KCNA gene family expression in murine mesenteric resistance artery smooth muscle. J Physiol. 2004; 556: 29–42.[Abstract/Free Full Text]

This article has been cited by other articles:

				S. J. Fountain, A. Cheong, J. Li, N. Y. Dondas, F. Zeng, I. C. Wood, and D. J. Beech Kv1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2719 - H2725. [Abstract] [Full Text] [PDF]

				W. C. Cole, F. Plane, and R. Johnson Letter to the Editor: Role of Kv1 Channels in Control of Arterial Myogenic Reactivity to Intraluminal Pressure Circ. Res., July 8, 2005; 97(1): e1 - e1. [Full Text] [PDF]

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