Hypotonicity-induced TRPV4 function in renal collecting duct cells: modulation by progressive cross-talk with Ca2+-activated K+ channels.
The mouse cortical collecting duct (CCD) M-1 cells were grown to confluency on coverslips to assess the interaction between TRPV4 and Ca(2+)-activated K(+) channels. Immunocytochemistry demonstrated strong expression of TRPV4, along with the CCD marker, aquaporin-2, and the Ca(2+)-activated K(+) channels, the small conductance SK3 (K(Ca)2.3) channel and large conductance BKα channel (K(Ca)1.1). TRPV4 overexpression studies demonstrated little physical dependency of the K(+) channels on TRPV4. However, activation of TRPV4 by hypotonic swelling (or GSK1016790A, a selective agonist) or inhibition by the selective antagonist, HC-067047, demonstrated a strong dependency of SK3 and BK-α activation on TRPV4-mediated Ca(2+) influx. Selective inhibition of BK-α channel (Iberiotoxin) or SK3 channel (apamin), thereby depolarizing the cells, further revealed a significant dependency of TRPV4-mediated Ca(2+) influx on activation of both K(+) channels. It is concluded that a synergistic cross-talk exists between the TRPV4 channel and SK3 and BK-α channels to provide a tight functional regulation between the channel groups. This cross-talk may be progressive in nature where the initial TRPV4-mediated Ca(2+) influx would first activate the highly Ca(2+)-sensitive SK3 channel which, in turn, would lead to enhanced Ca(2+) influx and activation of the less Ca(2+)-sensitive BK channel.
Dept. of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, TX 77030, USA.
Min
M
Jin
Jonathan
J
Berrout
Ling
L
Chen
Roger G
RG
O'Neil
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D051399:Aquaporin 2 / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism*
C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; C496900:Kcnn3 protein, mouse; D051036:Large-Conductance Calcium-Activated Potassium Channels; C530602:N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide; D010455:Peptides; D051640:Small-Conductance Calcium-Activated Potassium Channels; D013449:Sulfonamides; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D001030:Apamin; C064719:iberiotoxin; D007930:Leucine; D002118:Calcium