Stimulation of the KATP channel by ADP and diazoxide requires nucleotide hydrolysis in mouse pancreatic beta‐cells.
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1. The mechanisms by which ADP and the hyperglycaemic compound diazoxide stimulate the activity of the ATP-regulated K+ channel (KATP channel) were studied using inside-out patches isolated from mouse pancreatic beta-cells maintained in tissue culture. 2. The ability of diazoxide and ADP to increase KATP channel activity declined with time following patch excision and no stimulation was observed after 15-40 min. 3. Activation of KATP channels by ADP required the presence of intracellular Mg2+. The stimulatory effect of ADP was mimicked by AMP but only in the presence of ATP. Replacement of ATP with the non-hydrolysable analogue beta, gamma-methylene ATP did not interfere with the ability of ADP to stimulate KATP channel activity. By contrast, enhancement of KATP channel activity was critically dependent on hydrolysable ADP and no stimulation was observed after substitution of alpha,beta-methylene ADP for standard ADP. 4. The ability of diazoxide to enhance KATP channel activity was dependent on the presence of both internal Mg2+ and ATP. Diazoxide stimulation of KATP channel activity was not observed after substitution of beta,gamma-methylene ATP for ATP. However, in the presence of ADP, at a concentration which in itself had no stimulatory action (10 microM), diazoxide was stimulatory also in the presence of the stable ATP analogue. 5. The stimulatory action of diazoxide on KATP channel activity in the presence of ATP was markedly enhanced by intracellular ADP. This potentia…
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In ATP-free medium, the KATP channel open probability in inside-out patches is 0.06, and the whole-cell conductance under comparable conditions is ~10 nS.
“In ATP-free medium, the open probability in inside-out patches is 0.06 (366). The whole-cell conductance measured under comparable conditions is ~10 nS (573).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [366]
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Self-citation
- Authors
- Larsson, O., Ammälä, C., Bokvist, K., Fredholm, B., & Rorsman, P.
- Affiliations
- University of Gothenburg (SE)
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 1993-04
- Volume
- 463
- Issue
- 1
- Pages
- 349-365
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC1175347
- OpenAlex
- W2079353263
- Cited by
- 84
- References
- 0
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 1 · 2012: 1
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- ATP-sensitive potassium channels, ADP, diazoxide, nucleotide hydrolysis, pancreatic beta cells, magnesium, AMP, ATP, open probability, channel open time, beta,gamma-methylene ATP, alpha,beta-methylene ATP, channel gating, insulin secretion, glucose-stimulated insulin secretion, channel desensitization
- MeSH terms
- Adenosine Diphosphate, Adenosine Triphosphate, Animals, Diazoxide, Electrophysiology, Hydrolysis, Islets of Langerhans, Kinetics, Magnesium, Nucleotides, Stimulation, Chemical, Time Factors, Potassium Channels, Mice, In Vitro Techniques
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