Mitochondria have its key role within the process of energy metabolism of cells. The organelles are engaged in the cell regulation as well as cell death and survival and it act as a determinant of necrosis and apoptosis (Hirofumi Nishida, Akio Matsumoto, Naohiro Tomono, Takahiro Hanakai, Shintaro Harada, Haruaki Nakaya, 2010). From past so many decades, a progress in the conceptual understanding of mitochondrial functions has been increased for performing such functions ion transportation, cell deaths, cells in metabolism and energy transduction process.
Mitochondrial ATP sensitive potassium channels such as mitoKATP channels are known as a key element of cardio protections. The studies have revealed that mitoKATP channels along with calcium activated potassium channels (BKCa) are available on an inner membrane of mitochondria in forms of mitoKCa channels. A high conductance of Ca2+ activated potassium channels has found as the mediator for cardio protection alongside the reperfusion or ischemia and also mitoKATP do the same task. These both the channels activate and increase the mitochondrial functioning to uptake potassium that is needed for the functioning of oxidative phosphorylation process.
2 Mitochondrial Ca2+-activated K+ channel
Some of the functions perform under some physiological condition and other functions can be activated in pathological conditions and also play an important role cardio protection. An inner membrane of mitochondria has identified K+ channel through mitoplast methods. It has been revealed that calcium activated potassium channels resembles the properties of surface membranes. MitoKCa channels were first identified in the mitochondria in 1993 and it has been argued that mitoKATP channel with the help of influx of K+ ions by mitoKCa channels accelerate electron transfers. Also it has been suggested that an opening of these channels talks about cardio-protection.
Table 1: Mitochondrial ion channels involved in cardio-protection
Source: Hirofumi Nishida, Akio Matsumoto, 2010
It has been researched before that presence of BKCa channel opener NS1619 creates a strong reason for reducing it in infarct size within the pharmacological preconditions of hearts of rabbit. Its affects can be provoked through using blockers of BKCa channel named as paxilline. It has been argued that whether Flavoprotein oxidation helps in regulating mitoKATP channels within intact cardiac myocytes. The studies have found that entry of potassium by using mitoKCa directs the net oxidation process of mitochondria in the same way as the channels of mitoKATP. An accumulation of mitochondrial Ca2 is satisfies through an activation of mitoKATP channels.
3 Structural and functional implications of calcium activated potassium channels
The mitoKCa channel plays an important role for transporting of K_ within the matrix and influx of these ions can be added through channel opener NS1619 of BKCa channel Toshiaki Sato, Tomoaki Saito, Noriko Saegusa and Haruaki Nakaya, 2004). These channels for K_ influx can speed up an electron transfer process by respiratory chains and then it can lead to oxidation process of mitochondria in case of uncompensated with the donors of electrons. It has been found that oxidative effects of opener NS1619 remain unaffected by the 5HD blockers of mitoKATP channels. Taking all the things together it has indicated that NS1619 triggers and paxilline slows down the process of mitiKCa channels without having any effect on cardiac channels such as mitoKATP channels.
Figure 1: figure showing the mechanism of protection intervened through mitochondrial ion channels.
Source: Hirofumi Nishida , Akio Matsumoto, Naohiro Tomono et al , 2010
4 Mitochondrial permeability transition pores for cardio protection
The presence of mPTP (mitochondrial permeability transition pore) has been found as a multi-protein complex that is formed between inner and outer membranes of mitochondria. These mPTP opens at the time of reperfusion within few minutes and it leads to myocardial injury. The barriers related to an opening of mPTP presents cardio protection which is as same as IPC. It is said that if IPC discusses about the cardio protection by means of activation of KCa then mPTP can be concerned . A causal relationship has been found between mPTP and high conductance KCa and it is very important step in preconditioning of cardiac protection. An opening of mPTP along with Atr has been eliminated through some beneficial effects of IPC in terms of cardipo protection for contractile functions. Also the beneficial effects of activation of high conductance KCa channel with NS have closed down for some purpose. mPTP plays a significant role for cardio protection because of activation of potassium activated calcium channels that are involved in some mitochondrial channels (Chun-Mei Cao, Qiang Xia, Qin Gao, Mai Chen and Tak-Ming Wong, 2004).
It is observed from the studies that higher and large conductance of calcium activated potassium channels (BK, BKCa) are located in excitable as well as nonexcitable cells and these are engaged in cellular functioning such as excitability of neuronal parts, repolarisation process, modulation of vascular parts, neurotransmitter releases, uterine, urinary bladder and gastrointestinal muscle tissues and many more. Due t the higher conductance, activation channels of BK channels has a strong effect on membrane potential. BK channels vary from potassium (K+) channels because of the high sensitivity to intracellular concentration of calcium ions (Ca2+) (Srinivas Ghatta, Deepthi Nimmagadda, Xiaoping Xu , Stephen T. O’Rourke,2006). These features have prepared BK channels ideal to give feedback regulators within cellular types through a decrease in an entry of voltage dependent Ca2+ through hyperpolarisation of potential membrane..
5 Conclusion
It can be concluded that the presence of BK channels has been known as a player of cytoprotective role at the time of any heart problem. Thus BK blockers are suggested to find in several situations such as an injury of ischemic reperfusions. It can be concluded that activators of BK channels are proved as useful for treating vascular dysfunction that are linked with disorders like coronary heart problems and strokes etcIt has been shown that reperfusion after getting ischemia leads to an opening of nonspecific pores within inner mitochondrial membranes that are termed as mitochondrial permeability transition pore (MPTP). It crates reasons to mitochondria to become capable in hydrolysing instead of using synthesising process of ATP. It is clear from the report that mitoKATP channels along with calcium activated potassium channels (BKCa) are available on an inner membrane of mitochondria in forms of mitoKCa channels and these gives protection to cardiovascular system.
