Gluconate versus methanesulfonate

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JennaMo
JennaMo's picture
Gluconate versus methanesulfonate

What are the merits of using a gluconate-based intracellular solution over a menathsulfonate-based one? I am doing whole cell recording in a brain slice preparation and have been using K methanesulfonate but it has been suggested to me to try gluconate instead. I am planning to try it but would like some info on why it might be better. Thanks.

BigPharmBoy
BigPharmBoy's picture
Gluconate can inhibit various

Gluconate can inhibit various types of currents. Here is the link to the original articel:

http://www.ncbi.nlm.nih.gov/pubmed/9064651

However, methanesulfonate is a nasty mutagen which is probably why most people stay away from it.

moonillusion
moonillusion's picture
This original article is

This original article is really helpful!
I'm also making solutions and have been looking for the comparison of methanesulfonate vs. gluconate for quite a while. 

However, is there any evidence for the mutagenic effect of methanesulfonate anion? It scared me a little bit...
EMS is mutagenic mainly due to the ethyl group which reacts with guanine, not the methanesulfonate part of it. The anion form of methanesulfonate seems to be quite safe. 

the following link says,
"... it is highly corrosive in its acid form. In contrast, methanesulfonate anion (MSA) has extremely low inherent toxicity. MSA is fully biodegradable and naturally-occurring, being a key species in the atmospheric sulfur cycle."
http://www.arkema-inc.com/thiochemicals/anhydrous-methane-sulfonic-acid-amsa/amsa

And, "MSA is not genotoxic, not teratogenic"
http://www.arkema-inc.com/literature/pdf/987.pdf

BigPharmBoy
BigPharmBoy's picture
Upon going into the whole

Upon going into the whole cell configuration, the cell membrane is ruptured, resulting in degraded membrane lipids which may undergo lipid peroxidation by free radicals in the cell. One consequence of lipid peroxidation is the generation of ethane . Here is the link:

http://www.sciencemag.org/content/183/4121/208

Prior to the evolution of ethane, there will be alkyl precursors such as ethyl radicals that could very likely react with the methanesulfonate anion to form ethyl methanesulfonate. The methane sulfonate anion may be safe to handle, but it may not be so good for the cell when we take the dynamic nature of that immense universe into consideration. Of course, this is all speculation! :)

moonillusion
moonillusion's picture
Right. It makes sense.

Right. It makes sense.

Also, if you heat (>50C) methanesulfonic acid together with high concentration of ethanol, you will for sure get lots of EMS formation within hours.
(for example, 1M MSA + EtOH with no water at 70C, 0.25% conversion or 2500 ppm after 10 hours.)
http://www.pqri.org/workshops/Sulfonate/imagespdfs/Sulfonate_Esters_Webinar.pdf
So handling is not 100% safe.... but seems to be safe enough to work with.

Timmer
Timmer's picture
Beware using methylsulphate

Beware using methylsulphate if studying drugs affecting modulatory transission: it will massively alter 2nd messenger effects, for instance cAMP-dependent signalling. I've noticed this personally in recordings of the slow afterhyperpolarisation potential in rat HC. The current should usually be completely abolished by 5 uM isproterenol in the bath solution, but with methylsulphate you only get around a 50% reduction.

Timmer
Timmer's picture
Not convinced that gluconate

Not convinced that gluconate causes run-down of SiAHP as suggested in the abstract to that article! We record that current using gluconate (because of problems with methylsulphate and 2nd-messanger transmission), and get stable sIAHP amplitude over the course of 1hr+. We do however record smaller currents when using gluconate than with methylsulphate.