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July 05-06, 2019 | Paris, France
Pharmaceutics and Advanced Drug Delivery Systems
2nd International Conference and Exhibition on
Asian Journal of Biomedical and Pharmaceutical Sciences | ISSN:2249-622X | Volume 9
KATP channels openers are capable of brain mitochondria KATP channel opening on
nanomolar scale independent of MgATPase activity
Olga V Akopova, Kolchinskaya LI, Nosar VI, Mankovska IN and Sagach VF
AA Bogomoletz Institute of Physiology, Ukraine
In CNS mitochondrial KATP channel (mKATP channel) is
a promising target for the protection of neurons under
metabolic stress conditions. While it is generally assumed
that pharmacological mKATP channels openers (KCOs)
require MgATPase activity for mKATP channel opening,
literary data regarding this issue are controversial. Thus, we
studied the effect of most used KCOs, diazoxide and pinacidil,
on mKATP channel activity in isolated brain mitochondria in
the absence and the presence of MgATP. Using light scattering
technique, we obtained strong evidence that MgATP complex
is dispensable for mKATP channel activation by KCOs and
established high sensitivity of brain mKATP channel to these
openers with full activation at <0.5 µMof KCOs. Neither Mg 2+,
nor ATP alone affected the channels affinity to the drugs, but
MgATP shifted it to conventional micromolar concentrations.
To assure full channel activation, it was specifically blocked
by MgATP with consequent activation by KCOs in micromolar
range. The blocking of the activated channel by glibenclamide
and 5-hydroxydecanoate gave the same estimate of maximal
channel activity proving KCOs’ ability to elicit full activation on
nanomolar scale without MgATP. Based on our experiments
we came to the following conclusions: 1) native KATP channels
of brain mitochondria are highly sensitive to diazoxide
and pinacidil, which open KATP channel independent of
MgATPase activity on nanomolar concentration scale; 2)
neither Mg2+, nor ATP alone affected the mKATP channels
affinity to KATP channels openers, but the presence of MgATP
shifted it to much higher micromolar concentrations of the
drugs; 3) native brain mKATP channel might comprise the
sites with high affinity to diazoxide and pinacidil screened
by the binding of MgATP. Obtained results indicate novel
common features in the mechanismof native mKATP channel
activation by pharmacological openers that would help bring
new insight into understanding of mKATP channel properties.
Speaker Biography
Olga V Akopova has completed her PhD in 1997 and a Doctor of
Sciences Degree in Biochemistry in 2016. Now she is a principal
investigator at Circulation department of AA Bogomoletz Institute
of Physiology, Ukraine. Research interests: mitochondrial potassium
transport; the impact of K + transport on mitochondrial bioenergetics
and metabolism; mKATP channels, their properties and cell-specific
functions. She published a number of well cited research works devoted
to the study of bioenergetic and functional effects of mKATP channel
opening in brain and liver mitochondria. At present her interest is
focused on the study of pharmacological properties of mKATP channels
and their interactions with physiological ligands. She is the author of
about 35 research works indexed in MEDLINE and Scopus databases.
e:
Olga V Akopova et al., Asian J Biomed Pharmaceut Sci, | ISSN: 2249-622X
Volume 9