Cardiovascular K_ATP channels and advanced aging

Abstract

With advanced aging, there is a decline in innate cardiovascular function. This decline is not general in nature. Instead, specific changes occur that impact the basic cardiovascular function, which include alterations in biochemical pathways and ion channel function. This review focuses on a particular ion channel that couple the latter two processes, namely the KATP channel, which opening is promoted by alterations in intracellular energy metabolism. We show that the intrinsic properties of the KATP channel changes with advanced aging and argue that the channel can be further modulated by biochemical changes. The importance is widespread, given the ubiquitous nature of the KATP channel in the cardiovascular system where it can regulate processes as diverse as cardiac function, blood flow and protection mechanisms against superimposed stress, such as cardiac ischemia. We highlight questions that remain to be answered before the KATP channel can be considered as a viable target for therapeutic intervention.

Gene expression profiles of ion channels and receptors in mouse resistance arteries: Effects of cell type, vascular bed, and age

“…Endothelial cells had increased Kcnj8 (K ir 6.1) expression in Old vs Young. K ir 6.1 subunits are a critical component of K ATP channels, which are impaired in some arteries during aging, suggesting that an increase in K ir 6.1 may alter the function of K ATP channels with advanced age. All 22 other significant differences in gene expression in Old vs Young were observed in just 1 of the 4 sample groups tested.…”

“…Agewise comparisons yielded the lowest proportion of differentially expressed genes (Figures 1 and 2 99 suggesting that an increase in K ir 6.1 may alter the function of K ATP channels with advanced age. All 22 other significant differences in gene expression in Old vs Young were observed in just 1 of the 4 sample groups tested.…”

Electro-metabolic signaling

“…It is possible that age-related alterations to intercellular signaling (for example, due to the loss of cardiac and vascular K ATP channel function that has been documented in older animals [ Yang et al, 2016 ]) could be a proximate cause that deranges the metabolic sensing or signal transmission aspects of EMS, which would then be expected to contribute further to the aging process. It is not difficult to conceive that the reduced substrate delivery emanating from impaired blood flow regulation due to loss of EMS could then play into mitochondrial dysfunction and thus exert an outsized impact on cellular energy status.…”

Functional protection against cardiac diseases depends on ATP‐sensitive potassium channels

“…These mutations, in turn, increases the occurrence of ventricular arrhythmias (VA) in dilated cardiomyopathy patients. Moreover, a KCNJ8 mutation was also found to be associated with atrial fibrillation (AF), and K ATP channel currents were found to be decreased during chronic human AF …”

“…Moreover, a KCNJ8 mutation was also found to be associated with atrial fibrillation (AF), and K ATP channel currents were found to be decreased during chronic human AF. 31 Feng et al 32…”