Voltage-gated and stretch-activated potassium channels in the human heart

Abstract

Ion channels are essential for electrical signaling and contractility in cardiomyocytes. Detailed knowledge about the molecular function and regulation of cardiac ion channels is crucial for understanding cardiac physiology and pathophysiology especially in the field of arrhythmias. This review aims at providing a general overview on the identity, functional characteristics, and roles of voltage-gated as well as stretch-activated potassium selective channels in the heart. In particular, we will highlight potential therapeutic targets as well as the emerging fields of future investigations.

Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation

“…As a result, these mechanical forces are converted into electrochemical signals in the cells. Mechanosensitive ion channels are divided into 2 groups [32] . One is the non-selective depolarizing stretch-activated ion channel (SAC), which allows the influx of cations such as Ca 2+ , Na + , and K + into the cell in response to mechanical or hypo-osmotic stress.…”

“…The other one is the selective hyperpolarizing potassium channel, which includes the voltage-gated potassium channel (VGCs K ) and stretch-activated potassium channel (SACs K ). The pore in the VGCs K channel opens or closes depending upon the voltage in response to alteration of membrane potential due to the influx of a charged species, such as Ca 2+ , but does not directly open or close when mechanical stress is applied [32] , [33] . SACs K channels are activated by mechanical stimuli and include TREK-1, TREK-2, and TRAAK, which have 4 transmembrane segments and 2 pore domains [32] , [35] .…”

“…The pore in the VGCs K channel opens or closes depending upon the voltage in response to alteration of membrane potential due to the influx of a charged species, such as Ca 2+ , but does not directly open or close when mechanical stress is applied [32] , [33] . SACs K channels are activated by mechanical stimuli and include TREK-1, TREK-2, and TRAAK, which have 4 transmembrane segments and 2 pore domains [32] , [35] . TREK and TRAAK stand for TWIK-related K + (TREK) and TWIK-related arachidonic acid-activated K + channels, respectively; and TWIK is the abbreviation for the tandem two-pore K + domains in a weak inwardly rectifying K + channel [32] , [35] .…”

Cardiac fibroblasts

“…However, the role of ion channels in non-electrophysiological events, such as immunological responses or proliferation and migration of cancer cells, was appreciated only in the 1980s, when patch clamp techniques became generally available (for a review, see [49]). Interestingly, mechanosensitive channels are also involved in many forms of cancer (see review in this issue [50]). Besides controlling membrane potential, ion channels in concert with pumps and transporters regulate cellular calcium homeostasis, thereby affecting cell metabolism via this ubiquitous intracellular transmitter.…”

Advances in cardiac cellular electrophysiology – Relevance for clinical translation

“…On the other hand, some primarily voltage-sensitive channels such as ATP-inactivated K + channels (KATP), voltage-dependent, ultra-rapidly activating K + channels (Kv1.5) and different inwardly rectifying K + channels are merely modulated by stretch. Consequently, the next article discusses the role of voltage-dependent K + channels and stretch-activated channels in regulating the cardiac resting membrane potential and the final phase of repolarization, and how their dysfunction in cardiac disease may lead to arrhythmias [8].…”