Tags

Type your tag names separated by a space and hit enter

Combined modulation of the mitochondrial ATP-dependent potassium channel and the permeability transition pore causes prolongation of the biphasic calcium dynamics.
Cell Calcium 2006; 39(5):387-400CC

Abstract

The permeability transition pore (PTP) and the ATP-dependent potassium (mtK-ATP) channel of mitochondria are known to play key roles in mitochondrially mediated apoptosis. We investigated how modulation of the permeability transition pore (PTP) and the ATP-dependent potassium (mtK-ATP) channel, either as single elements or in combination, affects the proapoptotic intracellular calcium ([Ca(2+)](i)) transients and the mitochondrial membrane potential (psi(m)). For this purpose a model was established exploring the [Ca(2+)](i) transients in N2A cells using continuous application of ATP that causes a biphasic [Ca(2+)](i) response. This response was sensitive to endoplasmatic reticulum (ER) Ca(2+) depletion and a smooth ER Ca(2+)-ATPase (SERCA) antagonist. PTP inhibition by cyclosporine A (CsA) or its non-immunosuppressive derivative NIM811 caused an amplification of the secondary [Ca(2+)](i) peak and induced a hyperpolarization of psi(m). Both the putative mtK-ATP channel inhibitor 5-hydroxydecanoate (5-HD) and the opener diazoxide ameliorated the ATP-induced secondary [Ca(2+)](i) peak. The effect of diazoxide was accompanied by a depolarization of psi(m) whereas 5-HD had no effect on psi(m). When diazoxide and CsA or NIM811 were applied together the secondary [Ca(2+)](i) rise did not return to baseline and a not significant hyperpolarization of psi(m) was observed. So, simultaneous inhibition of PTP and activation of the mtK-ATP channel prevents the increased slope of the secondary [Ca(2+)](i) peak induced by CsA (or NIM811) and also the depolarization after diazoxide application. Hence, we propose that modulation of one of these channels leads to functional changes of the other channel by means of Delta[Ca(2+)](i) and Deltapsi(m).

Authors+Show Affiliations

Institute of Medical Neurobiology, Otto-von-Guericke University Magdeburg, Leipzigerstr. 44, D-39120 Magdeburg, Germany. yuliya.dahlem@medizin.uni-magdeburg.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16513166

Citation

Dahlem, Yuliya A., et al. "Combined Modulation of the Mitochondrial ATP-dependent Potassium Channel and the Permeability Transition Pore Causes Prolongation of the Biphasic Calcium Dynamics." Cell Calcium, vol. 39, no. 5, 2006, pp. 387-400.
Dahlem YA, Wolf G, Siemen D, et al. Combined modulation of the mitochondrial ATP-dependent potassium channel and the permeability transition pore causes prolongation of the biphasic calcium dynamics. Cell Calcium. 2006;39(5):387-400.
Dahlem, Y. A., Wolf, G., Siemen, D., & Horn, T. F. (2006). Combined modulation of the mitochondrial ATP-dependent potassium channel and the permeability transition pore causes prolongation of the biphasic calcium dynamics. Cell Calcium, 39(5), pp. 387-400.
Dahlem YA, et al. Combined Modulation of the Mitochondrial ATP-dependent Potassium Channel and the Permeability Transition Pore Causes Prolongation of the Biphasic Calcium Dynamics. Cell Calcium. 2006;39(5):387-400. PubMed PMID: 16513166.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined modulation of the mitochondrial ATP-dependent potassium channel and the permeability transition pore causes prolongation of the biphasic calcium dynamics. AU - Dahlem,Yuliya A, AU - Wolf,Gerald, AU - Siemen,Detlef, AU - Horn,Thomas F W, Y1 - 2006/03/02/ PY - 2005/04/20/received PY - 2005/11/30/revised PY - 2006/01/05/accepted PY - 2006/3/4/pubmed PY - 2006/6/29/medline PY - 2006/3/4/entrez SP - 387 EP - 400 JF - Cell calcium JO - Cell Calcium VL - 39 IS - 5 N2 - The permeability transition pore (PTP) and the ATP-dependent potassium (mtK-ATP) channel of mitochondria are known to play key roles in mitochondrially mediated apoptosis. We investigated how modulation of the permeability transition pore (PTP) and the ATP-dependent potassium (mtK-ATP) channel, either as single elements or in combination, affects the proapoptotic intracellular calcium ([Ca(2+)](i)) transients and the mitochondrial membrane potential (psi(m)). For this purpose a model was established exploring the [Ca(2+)](i) transients in N2A cells using continuous application of ATP that causes a biphasic [Ca(2+)](i) response. This response was sensitive to endoplasmatic reticulum (ER) Ca(2+) depletion and a smooth ER Ca(2+)-ATPase (SERCA) antagonist. PTP inhibition by cyclosporine A (CsA) or its non-immunosuppressive derivative NIM811 caused an amplification of the secondary [Ca(2+)](i) peak and induced a hyperpolarization of psi(m). Both the putative mtK-ATP channel inhibitor 5-hydroxydecanoate (5-HD) and the opener diazoxide ameliorated the ATP-induced secondary [Ca(2+)](i) peak. The effect of diazoxide was accompanied by a depolarization of psi(m) whereas 5-HD had no effect on psi(m). When diazoxide and CsA or NIM811 were applied together the secondary [Ca(2+)](i) rise did not return to baseline and a not significant hyperpolarization of psi(m) was observed. So, simultaneous inhibition of PTP and activation of the mtK-ATP channel prevents the increased slope of the secondary [Ca(2+)](i) peak induced by CsA (or NIM811) and also the depolarization after diazoxide application. Hence, we propose that modulation of one of these channels leads to functional changes of the other channel by means of Delta[Ca(2+)](i) and Deltapsi(m). SN - 0143-4160 UR - https://www.unboundmedicine.com/medline/citation/16513166/Combined_modulation_of_the_mitochondrial_ATP_dependent_potassium_channel_and_the_permeability_transition_pore_causes_prolongation_of_the_biphasic_calcium_dynamics_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4160(06)00002-9 DB - PRIME DP - Unbound Medicine ER -