NFATc3 regulates BK channel function in murine urinary bladder smooth muscle

The nuclear factor of activated T-cells (NFAT) is a Ca2+- dependent transcription factor that has been reported to regulate the expression of smooth muscle contractile proteins and ion channels. Here we report that large conductance Ca2+-sensitive potassium (BK) channels and voltage-gated K+ (KV) channels may be regulatory targets of NFATc3 in urinary bladder smooth muscle (UBSM). UBSM myocytes from NFATc3-null mice displayed a reduction in iberiotoxin (IBTX)-sensitive BK currents, a decrease in mRNA for the poreforming α-subunit of the BK channel, and a reduction in BK channel density compared with myocytes from wild-type mice. Tetraethylammonium chloride-sensitive KV currents were elevated in UBSM myocytes from NFATc3-null mice, as was mRNA for the Shab family member KV2.1. Despite KV current upregulation, bladder strips from NFATc3-null mice displayed an elevated contractile response to electrical field stimulation relative to strips from wild-type mice, but this difference was abrogated in the presence of the BK channel blocker IBTX. These results support a role for the transcription factor NFATc3 in regulating UBSM contractility, primarily through an NFATc3-dependent increase in BK channel activity. Copyright © 2008 the American Physiological Society.