(Tämä selvittäisi miksi suuret B1 annokset ovat edullisia Wernicken aivoturvotuksessa)
Arch Physiol Biochem. 1996 Oct;104(6):745-51.
Arch Physiol Biochem. 1996 Oct;104(6):745-51.
A non-cofactor role of thiamine derivatives in excitable cells?
Abstract
Thiamine diphosphate (TDP) is an important cofactor of pyruvate (PDH) and alpha-ketoglutarate (KGDH) dehydrogenases and transketolase.
Thiamine deficiency leads to reversible and irreversible brain lesions due to impaired oxidative metabolism.
A specific non-cofactor role for thiamine has also been proposed in excitable cells and thiamine triphosphate (TTP) might be involved in the regulation of ion channels.
Thiamine is taken up by neuroblastoma cells through a high affinity transporter. Inside the cells, it is rapidly phosphorylated to TDP. This high turnover TDP pool is the precursor for TTP. Most of the TDP however has a low turnover and is associated with PDH and KGDH in mitochondria. In excised inside-out patches from neuroblastoma cells, TTP, at a concentration of 1 microM, activates chloride channels of large unitary conductance, the so-called maxi-Cl- channels. These channels are inhibited by oxythiamine from the outide.
In addition to the role of TTP in the regulation of chloride channels, thiamine itself, or a presently unknown analog, may have trophic effects on neuronal cells.
Thiamine deficiency leads to reversible and irreversible brain lesions due to impaired oxidative metabolism.
A specific non-cofactor role for thiamine has also been proposed in excitable cells and thiamine triphosphate (TTP) might be involved in the regulation of ion channels.
Thiamine is taken up by neuroblastoma cells through a high affinity transporter. Inside the cells, it is rapidly phosphorylated to TDP. This high turnover TDP pool is the precursor for TTP. Most of the TDP however has a low turnover and is associated with PDH and KGDH in mitochondria. In excised inside-out patches from neuroblastoma cells, TTP, at a concentration of 1 microM, activates chloride channels of large unitary conductance, the so-called maxi-Cl- channels. These channels are inhibited by oxythiamine from the outide.
In addition to the role of TTP in the regulation of chloride channels, thiamine itself, or a presently unknown analog, may have trophic effects on neuronal cells.
- PMID:
- 8980789
- DOI:
- 10.1076/apab.104.6.745.12916
- [Indexed for MEDLINE]
- Tämä artikkeli tuo minulle uuden termin: maxi-Cl-channels. Haen tähän siitä lisätietoa: Tuo ylläoleva työhän on tehty neuroblastoomasolusta eikä normaalista neuronista.
- http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=131
- Maxi Cl- channels are high conductance, anion selective, channels initially characterised in skeletal muscle and subsequently found in many cell types including neurones, glia, cardiac muscle, lymphocytes, secreting and absorbing epithelia, macula densa cells of the kidney and human placenta syncytiotrophoblasts [9]. The physiological significance of the maxi Cl- channel is uncertain, but roles in cell volume regulation and apoptosis have been claimed. Evidence suggests a role for maxi Cl- channels as a conductive pathway in the swelling-induced release of ATP from mouse mammary C127i cells that may be important for autocrine and paracrine signalling by purines [4,8]. A similar channel mediates ATP release from macula densa cells within the thick ascending of the loop of Henle in response to changes in luminal NaCl concentration [2]. A family of human high conductance Cl- channels (TTYH1-3) that resemble Maxi Cl- channels has been cloned [11], but alternatively, Maxi Cl- channels have also been suggested to correspond to the voltage-dependent anion channel, VDAC, expressed at the plasma membrane [1,5].
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