NFATc3 regulates BK channel function in murine urinary bladder smooth muscle

Area of Science:

• Physiology
• Molecular Biology
• Urology

Background:

• Nuclear factor of activated T-cells (NFAT) is a calcium-dependent transcription factor involved in smooth muscle regulation.
• Specific NFAT isoforms and their roles in urinary bladder smooth muscle (UBSM) contractility are not fully understood.

Purpose of the Study:

• To investigate the role of NFATc3 in regulating ion channels and contractility in UBSM.
• To determine if large conductance Ca(2+)-sensitive potassium (BK) channels and voltage-gated K(+) (K(V)) channels are targets of NFATc3 in UBSM.

Main Methods:

• Utilized NFATc3-null mice and wild-type littermates.
• Performed electrophysiological recordings (e.g., IBTX-sensitive BK currents, tetraethylammonium chloride-sensitive K(V) currents) on UBSM myocytes.
• Quantified mRNA levels for BK channel alpha-subunit and K(V)2.1.
• Assessed contractile responses of bladder strips using electrical field stimulation.

Main Results:

• NFATc3-null UBSM myocytes showed reduced BK currents and BK channel density, with decreased BK channel alpha-subunit mRNA.
• Elevated K(V) currents and K(V)2.1 mRNA were observed in NFATc3-null UBSM myocytes.
• Bladder strips from NFATc3-null mice exhibited enhanced contractility, which was normalized by BK channel blockade.

Conclusions:

• NFATc3 plays a crucial role in regulating UBSM contractility.
• NFATc3 primarily enhances UBSM contractility by increasing BK channel activity.
• NFATc3 influences both BK and K(V) channel expression and function in UBSM.