Heteromeric Channels Formed From Alternating Kv7.4 and Kv7.5 a-Subunits Display Biophysical, Regulatory, and Pharmacological Characteristics of Smooth Muscle M-Currents. Journal Article

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Authors: Brueggemann, LI; Cribbs, LL; Byron, KL
Article Title: Heteromeric Channels Formed From Alternating Kv7.4 and Kv7.5 a-Subunits Display Biophysical, Regulatory, and Pharmacological Characteristics of Smooth Muscle M-Currents.
Abstract: Smooth muscle cells of the vasculature, viscera, and lungs generally express multiple a-subunits of the Kv7 voltage-gated potassium channel family, with increasing evidence that both Kv7.4 and Kv7.5 can conduct "M-currents" that are functionally important for the regulation of smooth muscle contractility. Although expression systems demonstrate that functional channels can form as homomeric tetramers of either Kv7.4 or Kv7.5 a-subunits, there is evidence that heteromeric channel complexes, containing some combination of Kv7.4 and Kv7.5 a-subunits, may represent the predominant configuration natively expressed in some arterial myocytes, such as rat mesenteric artery smooth muscle cells (MASMCs). Our previous work has suggested that Kv7.4/Kv7.5 heteromers can be distinguished from Kv7.4 or Kv7.5 homomers based on their biophysical, regulatory, and pharmacological characteristics, but it remains to be determined how Kv7.4 and Kv7.5 a-subunits combine to produce these distinct characteristics. In the present study, we constructed concatenated dimers or tetramers of Kv7.4 and Kv7.5 a-subunits and expressed them in a smooth muscle cell line to determine if a particular a-subunit configuration can exhibit the features previously reported for natively expressed Kv7 currents in MASMCs. Several unique characteristics of native smooth muscle M-currents were reproduced under conditions that constrain channel formation to a Kv7.4:Kv7.5 stoichiometry of 2:2, with alternating Kv7.4 and Kv7.5 a-subunits within a tetrameric structure. Although other subunit arrangements/combinations are not ruled out, the findings provide new insights into the oligomerization of a-subunits and the ways in which Kv7.4/Kv7.5 subunit assembly can affect smooth muscle signal transduction and pharmacological responses to Kv7 channel modulating drugs.
Journal Title: Frontiers in physiology
ISSN: 1664-042X; 1664-042X
Publisher: Unknown  
Date Published: 2020