NFATc3 regulates BK channel function in murine urinary bladder smooth muscle.
The nuclear factor of activated T-cells (NFAT) is a Ca(2+)-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 Ca(2+)-sensitive potassium (BK) channels and voltage-gated K(+) (K(V)) 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 pore-forming alpha-subunit of the BK channel, and a reduction in BK channel density compared with myocytes from wild-type mice. Tetraethylammonium chloride-sensitive K(V) currents were elevated in UBSM myocytes from NFATc3-null mice, as was mRNA for the Shab family member K(V)2.1. Despite K(V) 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.
Layne
J J
JJ
Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA.
Werner
M E
ME
Hill-Eubanks
D C
DC
Nelson
M T
MT
D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051669:Shab Potassium Channels / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
C496990:Kcnb1 protein, mouse; D051036:Large-Conductance Calcium-Activated Potassium Channels; D050778:NFATC Transcription Factors; C494009:Nfatc3 protein, mouse; D010455:Peptides; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D019789:Tetraethylammonium; C064719:iberiotoxin; D011188:Potassium