Measuring and evaluating the role of ATP-sensitive K+ channels in cardiac muscle

Abstract

Since ion channels move electrical charge during their activity, they have traditionally been studied using electrophysiological approaches. This was sometimes combined with mathematical models, for example with the description of the ionic mechanisms underlying the initiation and propagation of action potentials in the squid giant axon by Hodgkin and Huxley. The methods for studying ion channels also have strong roots in protein chemistry (limited proteolysis, the use of antibodies, etc). The advent of the molecular cloning and the identification of genes coding for specific ion channel subunits in the late 1980’s introduced a multitude of new techniques with which to study ion channels and the field has been rapidly expanding ever since (e.g. antibody development against specific peptide sequences, mutagenesis, the use of gene targeting in animal models, determination of their protein structures) and new methods are still in development. This review focuses on techniques commonly employed to examine ion channel function in a electrophysiological laboratory. The focus is on the KATP channel, but many of the techniques described are also used to study other ion channels.

Resistance of Fetal Guinea Pig Ventricular Myocardium to Hypoxia: Maintained Intracellular ATP Prevents the Opening of ATP-Sensitive Potassium Channels

“…The shortening of the action potential duration following a decline in oxygen support has been attributed to the opening of ATP-sensitive potassium channels. [8][9][10][11][12] We reported that the hypoxia-induced decline in action potential duration of the adult guinea pig ventricular myocardium was partially attenuated by the ATP-sensitive potassium channel blocker, glybenclamide. 13) Thus it was possible that the resistance of guinea pig fetal myocardium to hypoxia was due to a lack of the ATP-sensitive potassium channel.…”

“…7) The ATP-sensitive potassium channel is present in cardiomyocytes and is activated under hypoxic conditions and by pharmacological agents. [8][9][10][11][12] The ATP-sensitive potassium channel current (I KATP ) has a linear voltage dependence and thus generates a potent repolarizing power at depolarized membrane potentials. I KATP is responsible for the hypoxiainduced shortening of the myocardial action potential and decrease in contraction.…”

Antiapoptotic and insulin-releasing effects of zinc supplementation in type-1 diabetes through ATP sensitive potassium channels

“…[15] Bu bilgi çinkonun KATP'nin di¤er alt birimi olan SUR üzerinden kanal aktivitesini etkileyebilece¤ini düündürmektedir. Dahası SUR alt biriminin dahil oldu¤u ABC ailesi proteinlerinden [26] bazı üyeler Zn +2 taıyabilmektedir. [15] Dolayısıyla Zn +2 SUR'un bir substratı olarak kullanılıyor olabilir.…”

“…[15] Bu öngörümüz 2009 yılında yayınlanmı bir çalıma ile desteklenmektedir. [27] Bu çalımada, SUR1 insülin granüllerin ekzositozunda da önemli rol oynadı¤ı belirtilmitir. KATP kanalları hücre membranında çok, insülin granüllerinde daha çok bulunmaktadır.…”

“…Di¤er bir olasılık SUR1'in insülin salgılanmasındaki önemi alfa ve beta adacıklarında insülin vezikül trafi¤inin de rol alabilece¤idir. [27] ‹nsülin ve Zn +2 beta adacıklarından salgılandıktan sonra kan dolaımındaki yüksek pH'da Zn +2 ve insülin birbirinden ayırmaktadır. Çinko pankreasta bulunan alfa hücrelerindeki KATP kanallarını açarak hiperpolarizasyona neden olmakta ve glukagon salgısını azaltmaktadır.…”