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Ca²⁺-activated K⁺ channels are present in a wide variety of cells. We have previously reported the presence of small conductance Ca²⁺-activated K⁺ (SK or K_Ca) channels in human and mouse cardiac myocytes that contribute functionally toward the shape and duration of cardiac action potentials. Three isoforms of SK channel subunits (SK1, SK2, and SK3) are found to be expressed. Moreover, there is differential expression with more abundant SK channels in the atria and pacemaking tissues compared with the ventricles. SK channels are proposed to be assembled as tetramers similar to other K⁺ channels, but the molecular determinants driving their subunit interaction and assembly are not defined in cardiac tissues.

To investigate the heteromultimeric formation and the domain necessary for the assembly of 3 SK channel subunits (SK1, SK2, and SK3) into complexes in human and mouse …