Sci. STKE, 24 October 2000
Channels Sparking Relaxation
The large-conductance calcium-activated potassium channels (BK), composed of a pore-forming subunit and a β subunit, hyperpolarize smooth muscle cells and, thus, are important regulators of arterial vascular tone and blood pressure. The β1 isoform is expressed by the arterial vasculature and has been implicated in controlling the channel's sensitivity to calcium concentration, on the basis of coexpression studies. Brenner et al. created knockout mice for the β1 subunit and found that these mice had elevated blood pressure, enlarged hearts, and increased cerebral arterial tone under conditions of increased pressure. Electrophysiological analysis of cerebral artery myocytes indicated that the BK channels in the knockout mice had a decreased sensitivity to calcium. BK channel currents and calcium sparks (localized increases in calcium concentration caused by calcium released from the sarcoplasmic reticulum in response to a global calcium increase, see the commentary by Standen) were measured simultaneously. In myocytes from the the knockout mouse, calcium sparks frequently failed to activate the BK current and the BK currents induced were one-sixth as large as those in normal mouse myocytes. Thus, the β1 subunit plays an important role in the regulation of blood pressure, and the molecular mechanism for this regulation is to allow for the functional coupling of the BK channel to the calcium sparks to promote relaxation of the arterial smooth muscle.
Brenner, R. Peréz, G.J., Bonev, A.D., Eckman, D.M., Kosek, J.C., Wiler, S.W., Patterson, A.J., Nelson, M.T., and Aldrich, R.W. (2000) Vasoregulation by the β1 subunit of the calcium-activated potassium channel. Nature 407: 870-876. [Online Journal]
Standen, N. (2000) Tuning channels for blood pressure. Nature 407: 845-848. [Online Journal]
Citation: Sparking Relaxation. Sci. STKE 2000, tw3 (2000).
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