Regulatory mechanisms of mitochondrial BK<sub>Ca</sub> channels

González‐Cota, Ana Laura; Santana-Calvo, Carmen; Servín-Vences, Rocío; Orta, Gerardo; Balderas, Enrique

doi:10.1080/19336950.2021.1919463

Cited by 9 publications

(6 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of the BK Ca channel induces apoptosis after hypoxia-reoxygenation in NCM One of the major roles attributed to the activation of BK Ca channels is protecting adult cardiac cells and tissues from ischemia/hypoxia-reoxygenation injury [13,21,23,34]. These functions are specifically ascribed to the presence of BK Ca channels located in mitochondria of adult ventricular cardiomyocytes [21,34].…”

Section: Activation Of Bk Ca Channels In Neonatal Rat Heart Increases...mentioning

confidence: 99%

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury

et al. 2022

View full text Add to dashboard Cite

BKCa channels are large-conductance calcium and voltage-activated potassium channels that are heterogeneously expressed in a wide array of cells. Activation of BKCa channels present in mitochondria of adult ventricular cardiomyocytes is implicated in cardioprotection against ischemia-reperfusion (IR) injury. However, the BKCa channel’s activity has never been detected in the plasma membrane of adult ventricular cardiomyocytes. In this study, we report the presence of the BKCa channel in the plasma membrane and mitochondria of neonatal murine and rodent cardiomyocytes, which protects the heart on inhibition but not activation. Furthermore, K+ currents measured in neonatal cardiomyocyte (NCM) was sensitive to iberiotoxin (IbTx), suggesting the presence of BKCa channels in the plasma membrane. Neonatal hearts subjected to IR when post-conditioned with NS1619 during reoxygenation increased the myocardial infarction whereas IbTx reduced the infarct size. In agreement, isolated NCM also presented increased apoptosis on treatment with NS1619 during hypoxia and reoxygenation, whereas IbTx reduced TUNEL-positive cells. In NCMs, activation of BKCa channels increased the intracellular reactive oxygen species post HR injury. Electrophysiological characterization of NCMs indicated that NS1619 increased the beat period, field, and action potential duration, and decreased the conduction velocity and spike amplitude. In contrast, IbTx had no impact on the electrophysiological properties of NCMs. Taken together, our data established that inhibition of plasma membrane BKCa channels in the NCM protects neonatal heart/cardiomyocytes from IR injury. Furthermore, the functional disparity observed towards the cardioprotective activity of BKCa channels in adults compared to neonatal heart could be attributed to their differential localization.

show abstract

Section: Activation Of Bk Ca Channels In Neonatal Rat Heart Increases...mentioning

confidence: 99%

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, it is believed that in cardiomyocytes, BK Ca channels are present exclusively in mitochondria and are not found in the plasma membrane [ 11 , 105 ]. Here, we briefly present key findings that describe cardiac mitoBK Ca channels, and more details are presented in excellent papers [ 11 , 105 , 106 ].…”

Section: Mitochondrial Calcium-activated Potassium Channelsmentioning

confidence: 99%

Multidimensional Regulation of Cardiac Mitochondrial Potassium Channels

Kulawiak

Bednarczyk

Szewczyk

2021

Cells

View full text Add to dashboard Cite

Mitochondria play a fundamental role in the energetics of cardiac cells. Moreover, mitochondria are involved in cardiac ischemia/reperfusion injury by opening the mitochondrial permeability transition pore which is the major cause of cell death. The preservation of mitochondrial function is an essential component of the cardioprotective mechanism. The involvement of mitochondrial K+ transport in this complex phenomenon seems to be well established. Several mitochondrial K+ channels in the inner mitochondrial membrane, such as ATP-sensitive, voltage-regulated, calcium-activated and Na+-activated channels, have been discovered. This obliges us to ask the following question: why is the simple potassium ion influx process carried out by several different mitochondrial potassium channels? In this review, we summarize the current knowledge of both the properties of mitochondrial potassium channels in cardiac mitochondria and the current understanding of their multidimensional functional role. We also critically summarize the pharmacological modulation of these proteins within the context of cardiac ischemia/reperfusion injury and cardioprotection.

show abstract

“…However, there are many questions that still need to be answered regarding the detailed mechanism of how accessory subunits are directed and assembled in IMM and ONM, as well as the modulatory effect they exert on mitoBK and nBK. Regarding γ subunits, the association with the mitoBK-α and nBK-α is still to be addressed ( González-Cota et al, 2021 ).…”

Section: Biophysical Properties and Differences To Pmbkmentioning

confidence: 99%

BK in Double-Membrane Organelles: A Biophysical, Pharmacological, and Functional Survey

et al. 2021

View full text Add to dashboard Cite

In the 1970s, calcium-activated potassium currents were recorded for the first time. In 10years, this Ca2+-activated potassium channel was identified in rat skeletal muscle, chromaffin cells and characterized in skeletal muscle membranes reconstituted in lipid bilayers. This calcium- and voltage-activated potassium channel, dubbed BK for “Big K” due to its large ionic conductance between 130 and 300 pS in symmetric K+. The BK channel is a tetramer where the pore-forming α subunit contains seven transmembrane segments. It has a modular architecture containing a pore domain with a highly potassium-selective filter, a voltage-sensor domain and two intracellular Ca2+ binding sites in the C-terminus. BK is found in the plasma membrane of different cell types, the inner mitochondrial membrane (mitoBK) and the nuclear envelope’s outer membrane (nBK). Like BK channels in the plasma membrane (pmBK), the open probability of mitoBK and nBK channels are regulated by Ca2+ and voltage and modulated by auxiliary subunits. BK channels share common pharmacology to toxins such as iberiotoxin, charybdotoxin, paxilline, and agonists of the benzimidazole family. However, the precise role of mitoBK and nBK remains largely unknown. To date, mitoBK has been reported to play a role in protecting the heart from ischemic injury. At the same time, pharmacology suggests that nBK has a role in regulating nuclear Ca2+, membrane potential and expression of eNOS. Here, we will discuss at the biophysical level the properties and differences of mitoBK and nBK compared to those of pmBK and their pharmacology and function.

show abstract

Regulatory mechanisms of mitochondrial BK_Ca channels

Cited by 9 publications

References 111 publications

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury

Multidimensional Regulation of Cardiac Mitochondrial Potassium Channels

BK in Double-Membrane Organelles: A Biophysical, Pharmacological, and Functional Survey

Contact Info

Product

Resources

About

Regulatory mechanisms of mitochondrial BKCa channels

Cited by 9 publications

References 111 publications

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury

Multidimensional Regulation of Cardiac Mitochondrial Potassium Channels

BK in Double-Membrane Organelles: A Biophysical, Pharmacological, and Functional Survey

Contact Info

Product

Resources

About

Regulatory mechanisms of mitochondrial BK_Ca channels