Identification of a voltage-gated potassium channel in gerbil hippocampal mitochondria.
Transient cerebral ischemia is known to induce endogenous mechanisms that can prevent or delay neuronal injury, such as the activation of mitochondrial potassium channels. However, the molecular mechanism of this effect remains unclear. In this study, the single-channel activity was measured using the patch-clamp technique of the mitoplasts isolated from gerbil hippocampus. In 70% of all patches, a potassium-selective current with the properties of a voltage-gated Kv-type potassium channel was recorded with mean conductance 109+/-6pS in a symmetrical solution. The channel was blocked at negative voltages and irreversibly by margatoxin, a specific Kv1.3 channel inhibitor. The ATP/Mg(2+) complex and Ca(2+) ions had no effect on channel activity. Additionally, agitoxin-2, a potent inhibitor of voltage-gated potassium channels, had no effect on mitochondrial channel activity. This observation suggests that in contrast to surface membrane channels, the mitochondrial voltage-gated potassium channel could have a different molecular structure with no affinity to agitoxin-2. Western blots of gerbil hippocampal mitochondria and immunohistochemistry on gerbil brain sections confirmed the expression of the Kv1.3 protein in mitochondria. Our findings indicate that gerbil brain mitochondria contain a voltage-gated potassium channel that can influence the function of mitochondria in physiological and pathological conditions and that has properties similar to the surface membrane Kv1.3 channel.
Bednarczyk
Piotr
P
Department of Biophysics, Warsaw University of Life Sciences-SGGW, 159 Nowoursynowska St., 02-776 Warsaw, Poland. p.bednarczyk@nencki.gov.pl
Kowalczyk
Joanna E
JE
Beresewicz
Małgorzata
M
Dołowy
Krzysztof
K
Szewczyk
Adam
A
Zabłocka
Barbara
B
D000818:Animals; D005849:Gerbillinae; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D051664:Kv1.3 Potassium Channel / Q000032:analysis / Q000378:metabolism*; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000032:analysis / Q000378:metabolism*
D051664:Kv1.3 Potassium Channel; D024642:Potassium Channels, Voltage-Gated