Generation of Kcnma1(fl)-tdTomato, a conditional deletion of the BK channel alpha subunit in mouse

BK large conductance calcium-activated K+ channels (K(Ca)1.1) are expressed widely across many tissues, contributing to systemic regulation of cardiovascular, neurological, and other specialized physiological functions. The poreforming alpha 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 SM22 alpha- Cre; Kcnma1(fl/fl) mice, respectively. tdTomato expression was detected in Cre- expressing tissues, but not in Crenegative 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.