Pharmacology of mitochondrial potassium channels: dark side of the field.
Mitochondrial potassium channels play an important role in cytoprotection. Potassium channels in the inner mitochondrial membrane are modulated by inhibitors and activators (potassium channel openers) previously described for plasma membrane potassium channels. The majority of mitochondrial potassium channel modulators exhibit a broad spectrum of off-target effects. These include uncoupling properties, inhibition of the respiratory chain and effects on cellular calcium homeostasis. Therefore, the rational application of channel inhibitors or activators is crucial to understanding the cellular consequences of mitochondrial channel inhibition or activation. Moreover, understanding their side-effects should facilitate the design of a specific mitochondrial channel opener with cytoprotective properties. In this review, we discuss the complex interactions of potassium channel inhibitors and activators with cellular structures.
Szewczyk
Adam
A
Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland. adam@nencki.gov.pl
Kajma
Anna
A
Malinska
Dominika
D
Wrzosek
Antoni
A
Bednarczyk
Piotr
P
Zabłocka
Barbara
B
Dołowy
Krzysztof
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists* / Q000378:metabolism
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate