The M3 Receptor-mediated K+ Current (IKM3), a Gq Protein-coupled K+ Channel

Stimulation of muscarinic acetylcholine receptors (mAChRs) can activate an inward rectifier K+ current (IKACh), which is mediated by the M2 subtype of mAChR in cardiac myocytes. Recently, a novel delayed rectifier-like K+ current mediated by activation of the cardiac M3 receptors (designated IKM3) was identified, which is distinct from IKACh and other known K+ currents. While IKACh is known to be a Gi protein-gated K+ channel, the signal transduction mechanisms for IKM3 activation remained unexplored. We studied IKM3 with whole-cell patch clamp and macropatch clamp techniques. Whole cell IKM3 activated by choline persisted with minimal rundown over 2 h in presence of internal GTP. When GTP was replaced by guanyl-5′-yl thiophosphate, IKM3 demonstrated rapid and extensive rundown. While IKACh (induced by ACh) was markedly reduced in cells pretreated with pertussis toxin, IKM3 was unaltered. Intracellular application of antibodies targeting α-subunit of Gi/o protein suppressed IKACh without affecting IKM3. Antibodies targeting the N and the C terminus, respectively, of Gq protein α-subunit substantially depressed IKM3 but failed to alter IKACh. The antibody against β-subunits of G proteins inhibited both IKACh and IKM3. IKM3 activated by choline in the cell-attached mode of macropatches persisted in the cell-free configuration. Application of purified Gq protein α-subunit or βγ-subunit of G proteins or guanosine 5′-O-(thiotriphosphate) to the internal solution activated IKM3-like currents in inside-out patches. Our findings revealed a novel aspect of receptor-channel signal transduction mechanisms, and IKM3 represents the first Gq protein-coupled K+ channel. We propose that the G protein-coupled K+ channel family could be divided into two subfamilies: Gi protein-coupled K+ channel subfamily and Gq protein-coupled K+ channel subfamily. Stimulation of muscarinic acetylcholine receptors (mAChRs) can activate an inward rectifier K+ current (IKACh), which is mediated by the M2 subtype of mAChR in cardiac myocytes. Recently, a novel delayed rectifier-like K+ current mediated by activation of the cardiac M3 receptors (designated IKM3) was identified, which is distinct from IKACh and other known K+ currents. While IKACh is known to be a Gi protein-gated K+ channel, the signal transduction mechanisms for IKM3 activation remained unexplored. We studied IKM3 with whole-cell patch clamp and macropatch clamp techniques. Whole cell IKM3 activated by choline persisted with minimal rundown over 2 h in presence of internal GTP. When GTP was replaced by guanyl-5′-yl thiophosphate, IKM3 demonstrated rapid and extensive rundown. While IKACh (induced by ACh) was markedly reduced in cells pretreated with pertussis toxin, IKM3 was unaltered. Intracellular application of antibodies targeting α-subunit of Gi/o protein suppressed IKACh without affecting IKM3. Antibodies targeting the N and the C terminus, respectively, of Gq protein α-subunit substantially depressed IKM3 but failed to alter IKACh. The antibody against β-subunits of G proteins inhibited both IKACh and IKM3. IKM3 activated by choline in the cell-attached mode of macropatches persisted in the cell-free configuration. Application of purified Gq protein α-subunit or βγ-subunit of G proteins or guanosine 5′-O-(thiotriphosphate) to the internal solution activated IKM3-like currents in inside-out patches. Our findings revealed a novel aspect of receptor-channel signal transduction mechanisms, and IKM3 represents the first Gq protein-coupled K+ channel. We propose that the G protein-coupled K+ channel family could be divided into two subfamilies: Gi protein-coupled K+ channel subfamily and Gq protein-coupled K+ channel subfamily. While M2 receptors are commonly believed to be the only functional mAChRs 1The abbreviations used are: mAChR, muscarinic acetylcholine receptor; PLC, phospholipase C; PKC, protein kinase C; 4-DAMP, 4-diphenylacetoxy-N-methylpiperidine methiodide; GDPβS, guanyl-5′-yl thiophosphate; GTPγS, guanosine 5′-O-(thiotriphosphate); PTX, pertussis toxin; PIP2, phosphatidylinositol 4,5-bisphosphate; IP3, 1,4,5-inositol trisphosphate; DAG, diacylglycerol; OAG, 1-oleoyl-2-acetyl-sn-glycerol; PMA, phorbol 12-myristate 13-acetate; Bis, bisindolylmaleimide. 1The abbreviations used are: mAChR, muscarinic acetylcholine receptor; PLC, phospholipase C; PKC, protein kinase C; 4-DAMP, 4-diphenylacetoxy-N-methylpiperidine methiodide; GDPβS, guanyl-5′-yl thiophosphate; GTPγS, guanosine 5′-O-(thiotriphosphate); PTX, pertussis toxin; PIP2, phosphatidylinositol 4,5-bisphosphate; IP3, 1,4,5-inositol trisphosphate; DAG, diacylglycerol; OAG, 1-oleoyl-2-acetyl-sn-glycerol; PMA, phorbol 12-myristate 13-acetate; Bis, bisindolylmaleimide. in cardiac tissues, this concept has been challenged by recent findings revealing the presence of M3 receptors in the hearts of various species including guinea pig (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. H. Wang H. Wang Z. H. Yang B. Wang H. Wang Z. H. Wang H. Wang Z. and H. H. H. Wang Z. We that the cardiac M3 receptors the activation of a novel delayed rectifier K+ current IKM3) distinct from IKACh and other known K+ currents. IKACh is by inward IKM3 a delayed rectifier-like K+ We that M3 receptors and IKM3 a in cardiac and (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. The findings that are to of the to a to in of the of of with signal transduction and K+ H. Wang H. Wang Z. and M3 receptors are by of a a The M2 and are to an of and only a of IKACh is a G protein-gated K+ channel and activation is a of M2 receptors and K+ Gi proteins Y. activation of IKACh is by Gi protein and is of the of the Gi protein remained the M3 receptors activation of IKM3. M3 receptors been to activate the C kinase C that Gq protein a in IKM3 activation M3 in cardiac The was to this to the signal transduction mechanisms of activation of with and (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. H. Wang H. Wang Z. H. Yang B. Wang H. Wang Z. H. Wang H. Wang Z. The cells in and to with for of was by the of cells Y. Wang H. H. Yang B. Wang Z. clamp been in (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. H. Wang H. Wang Z. H. Yang B. Wang H. Wang Z. H. Wang H. Wang Z. The in the to K+ rapid delayed rectifier K+ and delayed rectifier K+ IKACh was activated in the presence of in the and the was the current the of the IKM3 was activated in the presence of choline in the and the was the currents of the delayed rectifier K+ current was in the presence of to IKM3 and IKACh Wang Z. current by to the cell currents in cell-attached and inside-out by from with of Z. Yang B. The solution and to with The solution and an of antibodies used in this from of the antibodies was by the Antibodies to the solution and by and the with and the the of of M3 and of was from in Z. Yang B. from was used a for and the of to are used for with or activated IKM3 in the presence of of M3 receptors by choline in the which was choline The current was to or G protein is for IKM3 activation by M3 GTP of the solution was replaced by a of to the GTP. and from to to by of GTP. in IKM3 rundown over a with a GTP with in the the current demonstrated a of whole-cell and a of G proteins for IKM3 is known that of M2 receptors the Gi which in with IKACh to the M2 receptors are to IKACh the Gi/o or in other IKACh is a Gi protein-gated K+ channel Y. Our this The of G proteins in was in IKACh was suppressed in cells pretreated with for in the IKM3 was unaltered. was by of antibody targeting the C of Gi/o protein α-subunit was to the of the cells by the with the antibody IKACh but IKM3 The from the the of Gi/o protein in the M2 receptors and of Gi/o protein to IKM3 activation by mAChR by antibodies into the of cells by solution been by other to the of Gq We used two and antibodies targeting the N and the of a Gq protein both and a of of IKACh was antibody to and the the antibody was by is that the of Gq protein is for with proteins Y. the from antibody the of Gq protein for IKM3 activation but to which Gq protein or the signal from M3 receptors to IKM3. is known that the N of Gq protein a for Y. Z. and βγ-subunit Y. The antibody is to the The of this antibody to IKM3 the of the α-subunit of Gq protein in with of Gq protein in IKM3 of antibody IKACh and IKM3. of IKM3 by antibodies for from to but IKACh antibody the IKM3 The the of antibody IKM3 of antibody targeting various β-subunits of G protein IKACh and IKM3. of both IKACh for and IKM3 for from to of various to the IKM3 are from cells for and OAG, or from antibody a of α-subunit of Gq protein for IKM3 the antibody the N of which is to be for and for βγ-subunit Y. Z. The βγ-subunit of Gi/o protein is known to a over α-subunit for IKACh activation Y. We studied the of various β-subunits including and IKM3. Our demonstrated the of antibody to both IKACh and IKM3 that be a functional in of Gq protein can in activation of that the phosphatidylinositol to 1,4,5-inositol and from in and the Our that antibody a phorbol of PKC, and a failed to IKM3 to the of for The of OAG, PMA, and with which to be by Wang Z. While application of the of with or the with or and the by The of was by that in the the K+ current by and the activation of with the findings Y. Wang H. H. Yang B. Wang Z. solution and current was inhibited by in the is that IKM3 activation was to was by the of of application of IKM3 the Gq protein and IKM3 is macropatch to the activation of IKM3. or IKM3 or IKACh was in cell-attached inside-out patches. of choline or to the failed to activate currents in the inside-out choline was in the a current of IKM3 was activated in the cell-attached patch and a into an inside-out patch the with was in the solution IKACh was in both cell-attached and inside-out When a of was in the but with choline and in the in the inside-out only currents activated in of and was activation of IKM3-like currents the internal was to IKM3-like currents in of with the that of are for to the IKM3-like currents from activated 2 was to the to the The of and IKM3-like currents of whole-cell IKACh and with and The from macropatch that IKM3 is activated by G protein in a of macropatch of IKACh and IKM3. of the currents activated by or choline and of the currents with the currents of inside-out patches. currents activated by in the in an inside-out patch IKM3-like current was in the presence of 2 to the activation of IKACh and IKM3-like currents by purified and activation of and IKM3-like currents by purified G IKM3-like current was in the presence of 2 to the the of and of G proteins in IKM3 the and proteins purified from cells with the and respectively, and the purified βγ-subunit of G proteins Application of to of the inside-out macropatch but failed to IKM3 in application of activated an IKM3-like current in but in of cells was IKACh by C and the other with the βγ-subunit of G protein activated IKACh current and IKM3 is that the signal M3 activation for but the signal is by both and the M3 signal transduction for in revealed a to was in this is that IKM3 activation by the M3 receptors is mediated by Gq the of for G protein be in the a cardiac M3 a of the to a for G protein the first of the which the G protein in cardiac to the of in the but only to and to the cardiac The an for the presence of Gq protein of the M3 in K+ channel is of K+ channel inward and G protein-gated K+ channel IKACh is a of the G protein-gated K+ channel family to and the only the cardiac currents to to a of the G protein-coupled K+ channel that K+ current is by G protein of G protein-coupled K+ from is that activation of G protein is for to other K+ channel K+ are by G protein activation is G Our that IKM3 is a Gq protein-coupled K+ channel can be an to the G protein-coupled K+ channel We propose that the G protein-coupled K+ channel family could be divided into two subfamilies: Gi protein-coupled K+ channel subfamily and Gq protein-coupled K+ channel has been to be in both and H. Wang H. Wang Z. IKM3 was to be H. Wang H. Wang Z. in with in both and the M2 M3 H. Wang H. Wang Z. and protein by in is to that an in IKM3 to and of are to this While M2 receptors are commonly believed to be the only functional mAChRs 1The abbreviations used are: mAChR, muscarinic acetylcholine receptor; PLC, phospholipase C; PKC, protein kinase C; 4-DAMP, 4-diphenylacetoxy-N-methylpiperidine methiodide; GDPβS, guanyl-5′-yl thiophosphate; GTPγS, guanosine 5′-O-(thiotriphosphate); PTX, pertussis toxin; PIP2, phosphatidylinositol 4,5-bisphosphate; IP3, 1,4,5-inositol trisphosphate; DAG, diacylglycerol; OAG, 1-oleoyl-2-acetyl-sn-glycerol; PMA, phorbol 12-myristate 13-acetate; Bis, bisindolylmaleimide. 1The abbreviations used are: mAChR, muscarinic acetylcholine receptor; PLC, phospholipase C; PKC, protein kinase C; 4-DAMP, 4-diphenylacetoxy-N-methylpiperidine methiodide; GDPβS, guanyl-5′-yl thiophosphate; GTPγS, guanosine 5′-O-(thiotriphosphate); PTX, pertussis toxin; PIP2, phosphatidylinositol 4,5-bisphosphate; IP3, 1,4,5-inositol trisphosphate; DAG, diacylglycerol; OAG, 1-oleoyl-2-acetyl-sn-glycerol; PMA, phorbol 12-myristate 13-acetate; Bis, bisindolylmaleimide. in cardiac tissues, this concept has been challenged by recent findings revealing the presence of M3 receptors in the hearts of various species including guinea pig (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. H. Wang H. Wang Z. H. Yang B. Wang H. Wang Z. H. Wang H. Wang Z. and H. H. H. Wang Z. We that the cardiac M3 receptors the activation of a novel delayed rectifier K+ current IKM3) distinct from IKACh and other known K+ currents. IKACh is by inward IKM3 a delayed rectifier-like K+ We that M3 receptors and IKM3 a in cardiac and (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. The findings that are to of the to a to in of the of of with signal transduction and K+ H. Wang H. Wang Z. The and M3 receptors are by of a a The M2 and are to an of and only a of IKACh is a G protein-gated K+ channel and activation is a of M2 receptors and K+ Gi proteins Y. activation of IKACh is by Gi protein and is of the of the Gi protein remained the M3 receptors activation of IKM3. M3 receptors been to activate the C kinase C that Gq protein a in IKM3 activation M3 in cardiac The was to this to the signal transduction mechanisms of activation of with and (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. H. Wang H. Wang Z. H. Yang B. Wang H. Wang Z. H. Wang H. Wang Z. The cells in and to with for of was by the of cells Y. Wang H. H. Yang B. Wang Z. clamp been in (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. H. Wang H. Wang Z. H. Yang B. Wang H. Wang Z. H. Wang H. Wang Z. The in the to K+ rapid delayed rectifier K+ and delayed rectifier K+ IKACh was activated in the presence of in the and the was the current the of the IKM3 was activated in the presence of choline in the and the was the currents of the delayed rectifier K+ current was in the presence of to IKM3 and IKACh Wang Z. current by to the cell currents in cell-attached and inside-out by from with of Z. Yang B. The solution and to with The solution and an of antibodies used in this from of the antibodies was by the Antibodies to the solution and by and the with and the the of of M3 and of was from in Z. Yang B. from was used a for and the of to are used for with or and (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. H. Wang H. Wang Z. H. Yang B. Wang H. Wang Z. H. Wang H. Wang Z. The cells in and to with for of was by the of cells Y. Wang H. H. Yang B. Wang Z. clamp been in (1Shi H. Wang H. Lu Y. Yang B. Wang Z. H. H. Lu Y. Yang B. Wang Z. H. Wang H. Wang Z. H. Yang B. Wang H. Wang Z. H. Wang H. Wang Z. The in the to K+ rapid delayed rectifier K+ and delayed rectifier K+ IKACh was activated in the presence of in the and the was the current the of the IKM3 was activated in the presence of choline in the and the was the currents of the delayed rectifier K+ current was in the presence of to IKM3 and IKACh Wang Z. current by to the cell currents in cell-attached and inside-out by from with of Z. Yang B. The solution and to with The solution and an of The antibodies used in this from of the antibodies was by the Antibodies to the solution and by and the with and the the of of M3 and of was from in Z. Yang B. from was used a for and the of to are used for with or activated IKM3 in the presence of of M3 receptors by choline in the which was choline The current was to or G protein is for IKM3 activation by M3 GTP of the solution was replaced by a of to the GTP. and from to to by of GTP. in IKM3 rundown over a with a GTP with in the the current demonstrated a of whole-cell and a of G proteins for IKM3 is known that of M2 receptors the Gi which in with IKACh to the M2 receptors are to IKACh the Gi/o or in other IKACh is a Gi protein-gated K+ channel Y. Our this The of G proteins in was in IKACh was suppressed in cells pretreated with for in the IKM3 was unaltered. was by of antibody targeting the C of Gi/o protein α-subunit was to the of the cells by the with the antibody IKACh but IKM3 The from the the of Gi/o protein in the M2 receptors and of Gi/o protein to IKM3 activation by mAChR by antibodies into the of cells by solution been by other to the of Gq We used two and antibodies targeting the N and the of a Gq protein both and a of of IKACh was antibody to and the the antibody was by is that the of Gq protein is for with proteins Y. the from antibody the of Gq protein for IKM3 activation but to which Gq protein or the signal from M3 receptors to IKM3. is known that the N of Gq protein a for Y. Z. and βγ-subunit Y. The antibody is to the The of this antibody to IKM3 the of the α-subunit of Gq protein in with from antibody a of α-subunit of Gq protein for IKM3 the antibody the N of which is to be for and for βγ-subunit Y. Z. The βγ-subunit of Gi/o protein is known to a over α-subunit for IKACh activation Y. We studied the of various β-subunits including and IKM3. Our demonstrated the of antibody to both IKACh and IKM3 that be a functional in of Gq protein can in activation of that the phosphatidylinositol to 1,4,5-inositol and from in and the Our that antibody a phorbol of PKC, and a failed to IKM3 to the of for The of OAG, PMA, and with which to be by Wang Z. While application of the of with or the with or and the by The of was by that in the the K+ current by and the activation of with the findings Y. Wang H. H. Yang B. Wang Z. solution and current was inhibited by in the is that IKM3 activation was to was by the of of application of IKM3 the Gq protein and IKM3 is macropatch to the activation of IKM3. or IKM3 or IKACh was in cell-attached inside-out patches. of choline or to the failed to activate currents in the inside-out choline was in the a current of IKM3 was activated in the cell-attached patch and a into an inside-out patch the with was in the solution IKACh was in both cell-attached and inside-out When a of was in the but with choline and in the in the inside-out only currents activated in of and was activation of IKM3-like currents the internal was to IKM3-like currents in of with the that of are for to the IKM3-like currents from activated 2 was to the to the The of and IKM3-like currents of whole-cell IKACh and with and The from macropatch that IKM3 is activated by G protein in a of macropatch of IKACh and IKM3. of the currents activated by or choline and of the currents with the currents of inside-out patches. currents activated by in the in an inside-out patch IKM3-like current was in the presence of 2 to the activation of IKACh and IKM3-like currents by purified and activation of and IKM3-like currents by purified G IKM3-like current was in the presence of 2 to the the of and of G proteins in IKM3 the and proteins purified from cells with the and respectively, and the purified βγ-subunit of G proteins Application of to of the inside-out macropatch but failed to IKM3 in application of activated an IKM3-like current in but in of cells was IKACh by C and the other with the βγ-subunit of G protein activated IKACh current and IKM3 is that the signal M3 activation for but the signal is by both and the M3 signal transduction for in revealed a to was in this is that IKM3 activation by the M3 receptors is mediated by Gq the of for G protein be in the a cardiac M3 a of the to a for G protein the first of the which the G protein in cardiac to the of in the but only to and to the cardiac The an for the presence of Gq protein of the M3 in K+ channel is of K+ channel inward and G protein-gated K+ channel IKACh is a of the G protein-gated K+ channel family to and the only the cardiac currents to to a of the G protein-coupled K+ channel that K+ current is by G protein of G protein-coupled K+ from is that activation of G protein is for to other K+ channel K+ are by G protein activation is G Our that IKM3 is a Gq protein-coupled K+ channel can be an to the G protein-coupled K+ channel We propose that the G protein-coupled K+ channel family could be divided into two subfamilies: Gi protein-coupled K+ channel subfamily and Gq protein-coupled K+ channel has been to be in both and H. Wang H. Wang Z. IKM3 was to be H. Wang H. Wang Z. in with in both and the M2 M3 H. Wang H. Wang Z. and protein by in is to that an in IKM3 to and of are to this activated IKM3 in the presence of of M3 receptors by choline in the which was choline The current was to or G protein is for IKM3 activation by M3 GTP of the solution was replaced by a of to the GTP. and from to to by of GTP. in IKM3 rundown over a with a GTP with in the the current demonstrated a of whole-cell and a of G proteins for IKM3 is known that of M2 receptors the Gi which in with IKACh to the M2 receptors are to IKACh the Gi/o or in other IKACh is a Gi protein-gated K+ channel Y. Our this The of G proteins in was in IKACh was suppressed in cells pretreated with for in the IKM3 was unaltered. was by of antibody targeting the C of Gi/o protein α-subunit was to the of the cells by the with the antibody IKACh but IKM3 The from the the of Gi/o protein in the M2 receptors and of Gi/o protein to IKM3 activation by mAChR by antibodies into the of cells by solution been by other We to the of Gq We used two and antibodies targeting the N and the of a Gq protein both and a of of IKACh was antibody to and the the antibody was by is that the of Gq protein is for with proteins Y. the from antibody the of Gq protein for IKM3 activation but to which Gq protein or the signal from M3 receptors to IKM3. is known that the N of Gq protein a for Y. Z. and βγ-subunit Y. The antibody is to the The of this antibody to IKM3 the of the α-subunit of Gq protein in with IKM3. The from antibody a of α-subunit of Gq protein for IKM3 the antibody the N of which is to be for and for βγ-subunit Y. Z. The βγ-subunit of Gi/o protein is known to a over α-subunit for IKACh activation Y. We studied the of various β-subunits including and IKM3. Our demonstrated the of antibody to both IKACh and IKM3 that be a functional in of Gq protein can in activation of that the phosphatidylinositol to 1,4,5-inositol and from in and the Our that antibody a phorbol of PKC, and a failed to IKM3 to the of for The of OAG, PMA, and with which to be by Wang Z. While application of the of with or the with or and the by The of was by that in the the K+ current by and the activation of with the findings Y. Wang H. H. Yang B. Wang Z. solution and current was inhibited by in the is that IKM3 activation was to was by the of of application of IKM3 the Gq protein and IKM3 is macropatch to the activation of IKM3. or IKM3 or IKACh was in cell-attached inside-out patches. of choline or to the failed to activate currents in the inside-out choline was in the a current of IKM3 was activated in the cell-attached patch and a into an inside-out patch the with was in the solution IKACh was in both cell-attached and inside-out When a of was in the but with choline and in the in the inside-out only currents activated in of and was activation of IKM3-like currents the internal was to IKM3-like currents in of with the that of are for to the IKM3-like currents from activated 2 was to the to the The of and IKM3-like currents of whole-cell IKACh and with and The from macropatch that IKM3 is activated by G protein in a the of and of G proteins in IKM3 the and proteins purified from cells with the and respectively, and the purified βγ-subunit of G proteins Application of to of the inside-out macropatch but failed to IKM3 in application of activated an IKM3-like current in but in of cells was IKACh by C and the other with the βγ-subunit of G protein activated IKACh current and IKM3 is that the signal M3 activation for but the signal is by both and the M3 signal transduction for in revealed a to was in this is that IKM3 activation by the M3 receptors is mediated by Gq the of for G protein be in the a cardiac M3 a of the to a for G protein the first of the which the G protein in cardiac to the of in the but only to and to the cardiac The an for the presence of Gq protein of the M3 in The K+ channel is of K+ channel inward and G protein-gated K+ channel IKACh is a of the G protein-gated K+ channel family to and the only the cardiac currents to to a of the G protein-coupled K+ channel that K+ current is by G protein of G protein-coupled K+ from is that activation of G protein is for to other K+ channel K+ are by G protein activation is G Our that IKM3 is a Gq protein-coupled K+ channel can be an to the G protein-coupled K+ channel We propose that the G protein-coupled K+ channel family could be divided into two subfamilies: Gi protein-coupled K+ channel subfamily and Gq protein-coupled K+ channel subfamily. IKACh has been to be in both and H. Wang H. Wang Z. IKM3 was to be H. Wang H. Wang Z. in with in both and the M2 M3 H. Wang H. Wang Z. and protein by in is to that an in IKM3 to and of are to this We Yang for

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.