GO:0008281 sulfonylurea receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0008281 sulfonylurea receptor activity describes the molecular function by which sulfonylurea drugs bind and modulate ATP-sensitive potassium (KATP) channels, primarily through the regulatory sulfonylurea receptor (SUR) subunits ABCC8 (SUR1) and ABCC9 (SUR2).
• Sulfonylurea receptor activity is not a catalytic activity but a drug-binding and regulatory function that controls KATP channel gating in response to intracellular nucleotides and pharmacological agents.
• The two major SUR isoforms, SUR1 and SUR2, differ in tissue distribution, nucleotide sensitivity, and pharmacology, which determines the therapeutic and side-effect profiles of sulfonylureas.
• Mutations in ABCC8 and ABCC9 cause neonatal diabetes, congenital hyperinsulinism, and other channelopathies that can be treated with sulfonylureas, making this activity clinically actionable.
• Beyond pancreatic beta cells, sulfonylurea receptor activity influences cardiac, neuronal, and vascular KATP channels, with implications for cardioprotection, neuroprotection, and cancer.
• Studying sulfonylurea receptor activity requires integrated approaches including electrophysiology, radioligand binding, CRISPR-based gene editing, and computational modeling to dissect drug–channel interactions.
Description
Sulfonylurea receptor activity (GO:0008281) is a molecular function that mediates the binding and pharmacological modulation of ATP-sensitive potassium (KATP) channels by sulfonylurea drugs such as glibenclamide and tolbutamide. These channels are hetero-octameric complexes composed of four inwardly rectifying potassium channel subunits (Kir6.x, encoded by KCNJ8 or KCNJ11) and four regulatory sulfonylurea receptor subunits (SUR1, encoded by ABCC8; SUR2, encoded by ABCC9). The SUR subunits are members of the ATP-binding cassette (ABC) transporter superfamily but function as regulatory sensors rather than transporters, coupling intracellular nucleotide levels to channel gating. Sulfonylurea receptor activity is therefore central to the physiological regulation of insulin secretion, vascular tone, and neuronal excitability, and it is the direct target of a major class of antidiabetic drugs. Researchers study this activity to understand KATP channel physiology, to develop isoform-selective therapeutics, and to explain adverse effects such as cardiac arrhythmias or hypoglycemia. The activity is also being explored in oncology, where glibenclamide-mediated targeting of SUR1 inhibits p70S6K and upregulates KLF4 to suppress non-small cell lung carcinoma.
sulfonylurea receptor activity At A Glance
| GO ID | GO:0008281 |
|---|---|
| GO term | sulfonylurea receptor activity |
| Ontology | biological_process |
| Synonym | None listed in QuickGO |
| Major function | Binding of sulfonylurea drugs and regulation of ATP-sensitive potassium (KATP) channel gating |
| Major proteins | SUR1 (ABCC8), SUR2 (ABCC9), Kir6.1 (KCNJ8), Kir6.2 (KCNJ11) |
| Tissue distribution | Pancreatic beta cells, cardiac myocytes, vascular smooth muscle, neurons |
| Clinical relevance | Target of antidiabetic sulfonylureas; mutations cause neonatal diabetes and hyperinsulinism |
| Research methods | Electrophysiology, radioligand binding, CRISPR knockout/knock-in, computational docking |
What Is GO:0008281?
Sulfonylurea receptor activity (GO:0008281) is the molecular function by which a protein binds sulfonylurea compounds and, in doing so, regulates the activity of an associated ATP-sensitive potassium channel. This function is intrinsic to the SUR subunits (SUR1/ABCC8 and SUR2/ABCC9) of KATP channels, which act as nucleotide sensors and drug receptors rather than as transporters. The activity encompasses the binding of sulfonylureas, the modulation of channel gating in response to these drugs, and the integration of intracellular Mg-ADP and ATP signals that control channel opening and closure.
Why Is sulfonylurea receptor activity Important in Cell Biology?
Sulfonylurea receptor activity is a linchpin of metabolic and cardiovascular physiology because it directly controls KATP channel opening, which in turn regulates insulin secretion, vascular tone, and cardiac stress responses. Pharmacologically, this activity is the target of sulfonylurea drugs used worldwide for type 2 diabetes, and it is also implicated in the mechanism of action of glibenclamide in cancer and stroke. Understanding the molecular details of sulfonylurea receptor activity is essential for designing isoform-selective drugs with fewer side effects, for interpreting genetic variants in ABCC8 and ABCC9, and for developing personalized therapies for KATP channelopathies.
• Sulfonylurea receptor activity is the primary mechanism by which sulfonylurea drugs stimulate insulin secretion in type 2 diabetes.
• Mutations in ABCC8 (SUR1) that alter sulfonylurea receptor activity cause neonatal diabetes mellitus and congenital hyperinsulinism.
• SUR2-containing KATP channels in the heart and vasculature modulate cardioprotection and vascular tone, making sulfonylurea receptor activity a cardiovascular drug target.
• Glibenclamide targeting of SUR1 inhibits p70S6K and upregulates KLF4 to suppress non-small cell lung carcinoma, linking sulfonylurea receptor activity to cancer biology.
• Sulfonylurea receptor activity in central pattern generating circuits affects neuronal network performance, as shown in Cancer borealis.
• The activity is regulated by intracellular Mg-ADP and ATP, and SUR2 acts as an intricate sensor for Mg-nucleotides.
• Epac2 has been proposed as an additional sulfonylurea receptor, expanding the scope of sulfonylurea receptor activity beyond KATP channels.
• Isoform-specific differences in sulfonylurea receptor activity determine drug efficacy and side effects, guiding personalized therapeutics.
• CRISPR-based models of ABCC8 and ABCC9 mutations enable precise dissection of sulfonylurea receptor activity in human cells.
• Sulfonylurea receptor activity is a paradigm for understanding how ABC transporter-like proteins can evolve regulatory functions.
What Happens During sulfonylurea receptor activity?
Sulfonylurea binding to SUR subunits
In simple terms: Sulfonylurea drugs bind to the SUR subunit of the KATP channel, like a key fitting into a lock.
Sulfonylurea receptor activity begins with the binding of sulfonylurea compounds (e.g., glibenclamide, tolbutamide) to the SUR1 or SUR2 subunit of the KATP channel complex. This binding occurs at the interface of the SUR subunit's transmembrane domains and is highly stereospecific. Radioligand binding studies have defined high-affinity sites for glibenclamide on SUR1 and lower-affinity sites on SUR2, which explains isoform-selective pharmacology. The binding event is the first step in a conformational cascade that ultimately closes the channel pore.
Nucleotide sensing and integration by SUR
In simple terms: SUR subunits sense the energy status of the cell by binding ATP and ADP, and this information is used to decide whether the channel should be open or closed.
SUR subunits contain two nucleotide-binding domains (NBD1 and NBD2) that bind Mg-ATP and Mg-ADP. Intracellular Mg-ADP binding to SUR stimulates channel opening, while ATP binding to Kir6.x inhibits it. Sulfonylureas modulate this nucleotide sensitivity by stabilizing a conformation that favors channel closure even in the presence of Mg-ADP. SUR2 is particularly sensitive to Mg-nucleotide levels, acting as an intricate sensor that fine-tunes KATP channel activity in cardiac and vascular tissues.
Conformational coupling to Kir6.x pore
In simple terms: When SUR changes shape after binding a drug or nucleotide, it pulls on the pore-forming Kir6.x subunits to open or close the channel.
The SUR subunit is physically associated with the Kir6.x pore-forming subunit in a 4:4 stoichiometry. Ligand binding to SUR induces conformational changes in its transmembrane domains that are transmitted to Kir6.x, altering the pore's open probability. This coupling is bidirectional: mutations in SUR that impair ATP hydrolysis or Mg-ADP binding can lock the channel in an open or closed state, leading to disease. The structural basis of this coupling is an active area of research using cryo-EM and electrophysiology.
Pharmacological modulation by sulfonylureas and KATP openers
In simple terms: Sulfonylureas close the channel, while other drugs (KATP openers) open it; both act through SUR.
Sulfonylureas such as glibenclamide inhibit KATP channel activity by increasing the channel's sensitivity to ATP and reducing its activation by Mg-ADP. In contrast, KATP channel openers (e.g., diazoxide, pinacidil) bind to SUR and promote channel opening, which is used clinically to treat hyperinsulinism. The balance between these opposing pharmacological effects determines the net KATP current and downstream cellular responses, such as insulin secretion or vascular relaxation. Isoform selectivity (SUR1 vs. SUR2) is a key determinant of drug action and side effects.
Downstream physiological effects
In simple terms: Closing or opening the KATP channel changes the cell's electrical activity, which controls insulin release, heart rhythm, and blood vessel tone.
In pancreatic beta cells, sulfonylurea-mediated closure of KATP channels depolarizes the membrane, triggers Ca2+ influx, and stimulates insulin secretion. In cardiac myocytes, SUR2-containing channels open during metabolic stress to shorten the action potential and protect against ischemia, but sulfonylureas can block this cardioprotection. In vascular smooth muscle, SUR2B-containing channels regulate tone, and sulfonylurea receptor activity influences blood pressure. In neurons, SUR1-containing channels modulate excitability and neurotransmitter release, as shown in central pattern generators of Cancer borealis.
Key Genes Involved in GO:0008281 sulfonylurea receptor activity
The genes encoding sulfonylurea receptor subunits and their associated potassium channel partners are listed below, with their roles in sulfonylurea receptor activity and research relevance.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ABCC8 | Encodes SUR1, the high-affinity sulfonylurea receptor in pancreatic beta cells and neurons | Mutations cause neonatal diabetes and hyperinsulinism; target for sulfonylurea therapy |
| ABCC9 | Encodes SUR2, the low-affinity sulfonylurea receptor in cardiac and vascular tissues | Mutations cause Cantu syndrome and cardiac arrhythmias; drug target for cardioprotection |
| KCNJ11 | Encodes Kir6.2, the pore-forming subunit of KATP channels in beta cells and neurons | Mutations cause neonatal diabetes; partner of SUR1 |
| KCNJ8 | Encodes Kir6.1, the pore-forming subunit in vascular smooth muscle | Mutations linked to Cantu syndrome; partner of SUR2 |
| EPAC2 | Encodes Epac2, a cAMP sensor proposed as an additional sulfonylurea receptor | Modulates insulin secretion; potential off-target of sulfonylureas |
| SLC2A2 | Encodes GLUT2, involved in glucose sensing upstream of KATP channels | Mutations cause Fanconi-Bickel syndrome; context for sulfonylurea activity |
| GCK | Encodes glucokinase, the glucose sensor in beta cells | Mutations cause MODY2; interacts with KATP channel activity |
| INS | Encodes insulin, the downstream effector of sulfonylurea-stimulated secretion | Readout for sulfonylurea receptor activity in beta cells |
| CACNA1A | Encodes a voltage-gated calcium channel involved in depolarization-induced secretion | Downstream of KATP closure; target for functional studies |
| KCNMA1 | Encodes BK channels that modulate beta-cell electrical activity | Cross-talk with KATP channels; potential modifier |
| P70S6K | Ribosomal protein S6 kinase, inhibited by glibenclamide via SUR1 in cancer | Readout for SUR1-mediated signaling in non-small cell lung carcinoma |
| KLF4 | Kruppel-like factor 4, upregulated by glibenclamide via SUR1 | Tumor suppressor; marker of SUR1-targeted cancer therapy |
| SUR1 | Protein name for ABCC8 gene product | Primary sulfonylurea receptor; drug target |
| SUR2 | Protein name for ABCC9 gene product | Secondary sulfonylurea receptor; cardiac and vascular roles |
| Kir6.1 | Protein name for KCNJ8 gene product | Pore-forming subunit in vascular KATP channels |
| Kir6.2 | Protein name for KCNJ11 gene product | Pore-forming subunit in pancreatic and neuronal KATP channels |
| Epac2 | cAMP-activated guanine nucleotide exchange factor | Proposed sulfonylurea receptor; modulates insulin granule exocytosis |
How Is sulfonylurea receptor activity Regulated?
Sulfonylurea receptor activity is regulated at multiple levels. Intracellular Mg-ADP and ATP levels directly control SUR nucleotide-binding domain occupancy and channel gating. Phosphorylation by protein kinases (e.g., PKA, PKC) can modulate SUR function and KATP channel activity. The expression levels of ABCC8 and ABCC9 are regulated transcriptionally and can be altered in disease states such as diabetes and heart failure. Additionally, Epac2 has been proposed to mediate some sulfonylurea effects independently of KATP channels, adding a layer of regulation through cAMP signaling. Pharmacological regulation by sulfonylureas and KATP openers is the basis for therapeutic intervention.
sulfonylurea receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ABCC8 | Neonatal diabetes mellitus, congenital hyperinsulinism | Knock-in mouse with patient mutation; iPSC-derived beta cells |
| ABCC9 | Cantu syndrome, cardiac arrhythmia | Cardiomyocyte-specific knockout; SUR2 knock-in mouse |
| KCNJ11 | Neonatal diabetes, DEND syndrome | Kir6.2 knockout; point-mutation knock-in |
| ABCC8 | Non-small cell lung carcinoma | SUR1 knockout in lung cancer cell lines; xenograft models |
| ABCC9 | Vascular smooth muscle dysfunction | Smooth muscle-specific SUR2 knockout; overexpression models |
Neonatal diabetes mellitus and congenital hyperinsulinism
Mutations in ABCC8 (SUR1) that impair sulfonylurea receptor activity cause neonatal diabetes mellitus, often with developmental delay (iDEND syndrome), while activating mutations cause congenital hyperinsulinism. Sulfonylurea therapy can successfully replace insulin in many patients with ABCC8 mutations, as demonstrated in two Iraqi siblings with iDEND syndrome who transitioned to sulfonylurea therapy. This highlights the clinical importance of understanding sulfonylurea receptor activity for personalized treatment.
Cardiovascular disease and cardioprotection
SUR2-containing KATP channels in cardiac myocytes open during ischemia to protect the heart, but sulfonylureas can block this cardioprotection, potentially increasing cardiovascular risk. A short form of SUR2 confers glibenclamide-insensitive KATP activity in the heart, suggesting that isoform-specific effects of sulfonylurea receptor activity are critical for cardiac safety. Personalized therapeutics for KATP-dependent pathologies must therefore consider the differential pharmacology of SUR1 and SUR2.
Cancer
Glibenclamide targets SUR1 to inhibit p70S6K activity and upregulate KLF4 expression, suppressing non-small cell lung carcinoma. This identifies sulfonylurea receptor activity as a potential therapeutic target in oncology, beyond its classical role in diabetes. The mechanism involves SUR1-dependent signaling that affects cell proliferation and differentiation.
Neurological and psychiatric disorders
SUR1-containing KATP channels in neurons modulate excitability and neurotransmitter release, and sulfonylurea receptor activity can alter central pattern generator performance, as shown in Cancer borealis. Dysregulation of KATP channels has been implicated in epilepsy, neuroprotection, and psychiatric conditions, although direct evidence for sulfonylurea receptor activity in these contexts is still emerging.
From sulfonylurea receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does a specific ABCC8 mutation alter sulfonylurea sensitivity? | Point-mutation knock-in in HEK293 or iPSC-derived beta cells |
| What is the effect of SUR1 loss on insulin secretion? | CRISPR knockout of ABCC8 in pancreatic beta cell lines or primary islets |
| Can SUR2 overexpression protect cardiomyocytes from ischemia? | Cardiomyocyte-specific overexpression of ABCC9 in mice |
| How does a tagged SUR1 behave in live cells? | Knock-in of fluorescent tag (e.g., GFP) at ABCC8 locus |
| Which genes modify sulfonylurea receptor activity? | Genome-wide CRISPR library screening in beta cells |
| Does glibenclamide affect cancer cell proliferation via SUR1? | SUR1 knockout in non-small cell lung carcinoma cell lines |
How to Study the sulfonylurea receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Patch-clamp electrophysiology | KATP channel current and gating | Functional assessment of sulfonylurea receptor activity |
| Radioligand binding | Drug binding affinity to SUR | Isoform selectivity profiling |
| CRISPR knockout | Loss-of-function effects on channel activity | Target validation in beta cells or cardiomyocytes |
| CRISPR knock-in | Effect of specific patient mutations | Modeling neonatal diabetes mutations |
| RNA-seq | Transcriptional changes downstream of SUR activation | Pathway analysis in cancer or beta cells |
| Proteomics | Protein interactions and post-translational modifications | Identifying SUR binding partners |
| Live-cell imaging | Subcellular localization and trafficking of SUR | Tagged knock-in models |
| CRISPR library screening | Genome-wide modifiers of drug response | Identifying synthetic lethal partners |
Electrophysiology
Patch-clamp recordings measure KATP channel currents in response to sulfonylureas and nucleotides, providing direct functional readout of sulfonylurea receptor activity. Inside-out and whole-cell configurations allow dissection of Mg-ADP and ATP sensitivity.
Radioligand binding assays
Binding of radiolabeled glibenclamide to SUR subunits quantifies affinity and isoform selectivity, which is essential for drug development. These assays can be performed on membrane preparations from cells expressing recombinant SUR1 or SUR2.
CRISPR-based gene editing
Knockout, knock-in, and point mutations in ABCC8, ABCC9, KCNJ11, and KCNJ8 allow causal testing of specific residues in sulfonylurea receptor activity. CRISPR screens can identify modifiers of drug response.
Computational modeling and docking
Molecular dynamics simulations and docking studies predict how sulfonylureas bind to SUR and how mutations affect drug efficacy, guiding experimental design. These methods complement structural biology approaches.
How CRISPR Can Be Used to Study GO:0008281 sulfonylurea receptor activity
Knockout
CRISPR knockout of ABCC8 or ABCC9 eliminates sulfonylurea receptor activity, allowing researchers to test the contribution of SUR1 or SUR2 to KATP channel function, insulin secretion, and drug responses. Knockout models are essential for validating target specificity of sulfonylureas.
Point Mutation
Introducing patient-specific point mutations (e.g., in ABCC8) via CRISPR base editing or homology-directed repair recreates disease alleles and tests their impact on sulfonylurea receptor activity and drug sensitivity. This approach is powerful for personalized medicine.
Knock-in
Knock-in of fluorescent or epitope tags at the endogenous ABCC8 or ABCC9 locus enables live-cell imaging and proteomic analysis of SUR subunits without overexpression artifacts. Knock-in of reporter genes can also monitor SUR expression in vivo.
Overexpression
Overexpression of wild-type or mutant SUR1/SUR2 in heterologous cells (e.g., HEK293) is used to study channel pharmacology and nucleotide sensitivity in isolation. This approach is useful for high-throughput drug screening.
How EDITGENE Supports sulfonylurea receptor activity Research
Researchers studying sulfonylurea receptor activity-related genes often need to determine whether a candidate gene is causally involved in KATP channel function, drug response, or disease. EDITGENE provides a comprehensive suite of CRISPR-based services to create precisely engineered cell models that answer these questions.
Contact EDITGENE today to design your custom CRISPR model for sulfonylurea receptor activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABCC9 Knockout HEK293 Cell Line | EDJ-KQ6881 | Human | 10060 | Details Get a Quote |
| ABCC8 Knockout HEK293 Cell Line | EDJ-KQ11943 | Human | 6833 | Details Get a Quote |
| ABCC8 Knockout A-549 Cell Line | EDJ-KQ40456 | Human | 6833 | Details Get a Quote |
| ABCC8 Knockout HeLa Cell Line | EDJ-KQ54591 | Human | 6833 | Details Get a Quote |
| ABCC9 Knockout HeLa Cell Line | EDJ-KQ55308 | Human | 10060 | Details Get a Quote |
| ABCC9 Knockout A-549 Cell Line | EDJ-KQ63791 | Human | 10060 | Details Get a Quote |
| ABCC8 Knockout HCT 116 Cell Line | EDJ-KQ71549 | Human | 6833 | Details Get a Quote |
| ABCC9 Knockout HCT 116 Cell Line | EDJ-KQ72248 | Human | 10060 | Details Get a Quote |
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Frequently Asked Questions About sulfonylurea receptor activity
What is sulfonylurea receptor activity?
Sulfonylurea receptor activity (GO:0008281) is the molecular function by which proteins such as SUR1 (ABCC8) and SUR2 (ABCC9) bind sulfonylurea drugs and regulate ATP-sensitive potassium (KATP) channel gating.
What genes are involved in sulfonylurea receptor activity?
The main genes are ABCC8 (SUR1), ABCC9 (SUR2), KCNJ11 (Kir6.2), and KCNJ8 (Kir6.1), which together form KATP channels.
How does sulfonylurea receptor activity regulate insulin secretion?
Sulfonylureas bind SUR1, close KATP channels, depolarize beta cells, and trigger calcium influx and insulin secretion.
What diseases are linked to sulfonylurea receptor activity?
Mutations in ABCC8 and ABCC9 cause neonatal diabetes, congenital hyperinsulinism, Cantu syndrome, and cardiac arrhythmias.
Can sulfonylureas be used to treat neonatal diabetes?
Yes, many patients with ABCC8 mutations can transition from insulin to sulfonylurea therapy, as shown in clinical case studies.
What is the difference between SUR1 and SUR2?
SUR1 (ABCC8) is found in pancreatic beta cells and neurons with high sulfonylurea affinity, while SUR2 (ABCC9) is in cardiac and vascular tissues with lower affinity and different nucleotide sensitivity.
How is sulfonylurea receptor activity studied in the lab?
Common methods include patch-clamp electrophysiology, radioligand binding, CRISPR knockout/knock-in, and computational modeling.
Is sulfonylurea receptor activity involved in cancer?
Yes, glibenclamide targeting SUR1 inhibits p70S6K and upregulates KLF4 to suppress non-small cell lung carcinoma.
What are the side effects of targeting sulfonylurea receptor activity?
Blocking SUR2-containing cardiac KATP channels may impair cardioprotection, and excessive insulin secretion can cause hypoglycemia.
Can CRISPR be used to model sulfonylurea receptor mutations?
Yes, CRISPR knockout, knock-in, and point mutation models in ABCC8 and ABCC9 allow precise study of disease mutations and drug responses.
Conclusion
Sulfonylurea receptor activity (GO:0008281) is a critical molecular function that governs KATP channel gating in response to sulfonylurea drugs and intracellular nucleotides. Its roles in insulin secretion, cardiovascular protection, neuronal excitability, and cancer make it a high-value target for both basic research and therapeutic development. Advances in CRISPR-based modeling and structural biology are poised to reveal isoform-specific mechanisms and enable personalized treatments for KATP channelopathies. Continued investigation of sulfonylurea receptor activity will likely yield new drugs with improved safety and efficacy.
References
- 1. Xu K et al.. 2019. Glibenclamide Targets Sulfonylurea Receptor 1 to Inhibit p70S6K Activity and Upregulate KLF4 Expression to Suppress Non-Small Cell Lung Carcinoma.. Mol Cancer Ther 18(11):2085-2096 PMID: 31341030
- 2. Boyd AE 3rd et al.. 1991. Sulfonylurea signal transduction.. Recent Prog Horm Res 47:299-316; discussion 316-7 PMID: 1660613
- 3. Nichols CG. 2023. Personalized Therapeutics for K(ATP)-Dependent Pathologies.. Annu Rev Pharmacol Toxicol 63:541-563 PMID: 36170658
- 4. Hou T et al.. 2024. Sulfonylurea receptor 2 (SUR2), intricate sensors for intracellular Mg-nucleotides.. Bioessays 46(3):e2300151 PMID: 38227376
- 5. Rehmann H. 2012. Epac2: a sulfonylurea receptor?. Biochem Soc Trans 40(1):6-10 PMID: 22260657
- 6. Kedia S et al.. 2024. Sulfonylurea Receptor Pharmacology Alters the Performance of Two Central Pattern Generating Circuits in Cancer borealis.. Function (Oxf) 5(6) PMID: 39293809
- 7. Ozsu E et al.. 2016. Successful transition to sulfonylurea therapy in two Iraqi siblings with neonatal diabetes mellitus and iDEND syndrome due to ABCC8 mutation.. J Pediatr Endocrinol Metab 29(12):1403-1406 PMID: 27849623
- 8. Pu JL et al.. 2008. Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity.. J Mol Cell Cardiol 44(1):188-200 PMID: 18001767
