摘要
There is accumulating evidence that the subfamily of large-conductance potassium (“big”, “BK”) channels are involved in diverse, and perhaps coordinated, protective or counteractive responses to local or generalized ischemia and hypoxia. Although widely distributed, the physiological differences among BK channels which results from posttranslational modification (alternative splicing) and co-assembly with auxiliary modulatory subunits (<em>β</em><sub>1-4</sub> and <em>γ</em><sub>1-4</sub>), bestows localized differences in subunit composition, distribution, 2<sup>nd</sup>-messenger coupling, and pharmacologic properties. Due to the ubiquitous nature of BK channels and the multiplicity of subtypes, they have many potential therapeutic applications in the maintenance of oxygen homeostasis, cerebro- and cardio-protection, and stimulation of respiration in response to drug-induced respiratory depression. BK channels may also offer other potentially broad and underrecognized promising targets for novel pharmaceutical development.
There is accumulating evidence that the subfamily of large-conductance potassium (“big”, “BK”) channels are involved in diverse, and perhaps coordinated, protective or counteractive responses to local or generalized ischemia and hypoxia. Although widely distributed, the physiological differences among BK channels which results from posttranslational modification (alternative splicing) and co-assembly with auxiliary modulatory subunits (<em>β</em><sub>1-4</sub> and <em>γ</em><sub>1-4</sub>), bestows localized differences in subunit composition, distribution, 2<sup>nd</sup>-messenger coupling, and pharmacologic properties. Due to the ubiquitous nature of BK channels and the multiplicity of subtypes, they have many potential therapeutic applications in the maintenance of oxygen homeostasis, cerebro- and cardio-protection, and stimulation of respiration in response to drug-induced respiratory depression. BK channels may also offer other potentially broad and underrecognized promising targets for novel pharmaceutical development.
作者
John F. Peppin
Joseph V. Pergolizzi
Alexander Kraus
Robert B. Raffa
John F. Peppin;Joseph V. Pergolizzi;Alexander Kraus;Robert B. Raffa(Marian University College of Osteopathic Medicine, Indianapolis, USA;Pikeville University College of Osteopathic Medicine, Pikeville Kentucky, USA;Enalare Therapeutics Inc., Princeton, USA;NEMA Research Inc., Naples, USA;Neumentum Inc., Morristown, USA;University of Arizona College of Pharmacy, Tucson, USA;Temple University School of Pharmacy, Philadelphia, USA)
