On Potential Interactions between Non-selective Cation Channel TRPM4 and Sulfonylurea Receptor SUR1

Abstract

Background: SUR1, the regulatory subunit of K ATP channels, was hypothesized to associate with TRPM4 to form novel channels, implicated in cell death following neurovascular trauma. Results: The properties of heterologously expressed TRPM4 channels are not modified by SUR1. Conclusion:The coupling between SUR1 and TRPM4 is unlikely. Significance: The roles of TRPM4 and K ATP channels in the pathogenesis of brain edema and hemorrhage should be reassessed.

The Sulfonylurea Receptor 1 (Sur1)-Transient Receptor Potential Melastatin 4 (Trpm4) Channel

“…FRET was not observed between C terminus-fused Sur1 and C terminus-fused Trpm4 (Fig. 1 B ), as found previously (20), although the two did co-associate, as found in co-immunoprecipitation experiments (Fig. 1 E ).…”

“…Overabundant expression of Trpm4 led to a dominance of Trpm4 at the cell membrane that was associated with reduced surface expression of Sur1. These observations likely account for the failure to demonstrate Sur1-Trpm4 channels in a recently published study (20). In that study, the expression conditions used were such that Trpm4 currents were very large.…”

TRPP2 and TRPV4 Form an EGF-Activated Calcium Permeable Channel at the Apical Membrane of Renal Collecting Duct Cells

“…The ability of this channel to conduct divalent cation and the higher occurrence rate in cilia (-) cells may result in chronic elevations of [Ca 2+ ] i in cilia (-) cells as has been previously reported [13]. Although we detected mRNAs of TRPP1, TRPP2, TRPV4, TRPM4, TRPM6, TRPC1 and TRPC2 in both cell types, however, this 23-pS channel exhibits distinct biophysical features compared to the individual TRP channels detected by RT-PCR, as well as to TRPV5 and TRPV6 [3–5,21–23,28–31]. We hypothesized that this channel might be a heterotetramer of TRPP2 and TRPV4.…”

“…However, the biophysical properties of this 23-pS channel are distinct from the individual channel mentioned above. TRPM4 can be inhibited by ATP and does not permeate to divalent cations [21]; TRPM6 has a single-channel conductance ~83-pS [22] and a much higher permeability to divalent cations [16]; TRPV5 and TRPV6 channels are characterized by voltage-dependent opening at negative potentials and extremely strong inward rectification with single-channel conductance of 75-90-pS and 40-70-pS, respectively [23,24]; TRPC1 channels are non-selective between Ba 2+ and Na + with a single-channel conductance of ~16-pS [23]; TRPC2 channels have significant higher permeability to divalent cation compared to the 23-pS channel and a single-channel conductance of ~42-pS [24]; TRPP2 channel has a single-channel conductance of 40-177-pS and can be blocked by amiloride [4]; the heteromeric TRPP2/TRPC1 channel complex functions as GPCR-activated channel with a single-channel conductance of ~40-pS [3–5]; finally, TRPV4 channels exhibits strong outward rectification with single-channel conductance of ~90-pS [25,26]. Therefore, based on the results obtained by Mn 2+ quenching assays (Figure 3d & 3e ) and the work of Kötten et al and Stewart et al [6,7] we focused on a potential interaction between TRPP2 and TRPV4.…”

Domain Organization of the ATP-sensitive Potassium Channel Complex Examined by Fluorescence Resonance Energy Transfer

“…Apparent FRET efficiency between nSUR1Y and different tagged and untagged Kir6.2 subunits (top), between nSUR1C and nSUR1Y with additional untagged subunits (center), between Kir6.2C and full-length SUR1Y (below, from Ref. 40), and between nSUR1Y and cSUR1C (bottom). CFPand YFP-tagged DNA constructs were expressed at 1:1 ratio in each case.…”