Generation of Kcnma1fl‐tdTomato, a conditional deletion of the BK channel α subunit in mouse

Physiological Reports

Betsir G. Zemen¹  Michael H. Lai¹  Joshua P. Whitt¹  Zulqarnain Khan¹  Guiling Zhao² 

[1] Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland;Center of BioMedical Engineering and Technology and Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland

关键词: BK channel;    calcium‐activated potassium channel;    Cre‐lox;    Kcnma1;    maxi K;    mSlo1;    potassium channel;    red fluorescent protein;    tandem dimer tomato;   

DOI  :  10.14814/phy2.12612

来源: Wiley

【 摘 要 】

Abstract

BK large conductance calcium-activated K⁺ channels (K_Ca1.1) are expressed widely across many tissues, contributing to systemic regulation of cardiovascular, neurological, and other specialized physiological functions. The pore-forming α subunit is encoded by the Kcnma1 gene, originally named mSlo1 in mouse and slowpoke in Drosophila. Global deletion in mouse (Kcnma1^−/−) produces a plethora of defects in neuron and muscle excitability, as well as other phenotypes related to channel function in nonexcitable cells. While homozygous null mice are viable, the ubiquitous loss of BK function has complicated the interpretation of phenotypes involving the interaction of multiple cell types which independently express BK channels. Here, we report the generation of a targeted allele for conditional inactivation of Kcnma1 using the Cre-loxP system (Kcnma1^fl-tdTomato). Cre-mediated recombination generates a null allele, and BK currents were not detectable in neurons and muscle cells from Nestin-Cre; Kcnma1^fl/fl and SM22α-Cre; Kcnma1^fl/fl mice, respectively. tdTomato expression was detected in Cre-expressing tissues, but not in Cre-negative controls. These data demonstrate the utility of Kcnma1^fl-tdTomato for conditional deletion of the BK channel, facilitating the understanding of tissue-specific contributions to physiological function in vivo.

【 授权许可】

CC BY   
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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