In central nervous system (CNS), ion channels, especially potassium channels play important regulatory roles in physiological
processes. Potassium (K+) channels (e.g., voltage-gated K+ channel, calcium-activated K+ channel) can be activated by
membrane potential shift as well as various ligands [1]. K+ channels have widely relationship with CNS diseases. Although
many studies have tried to reveal the effect of K+ channels in CNS diseases [2-5], the underlying mechanisms are not clearly
elucidated, because of the various subfamilies and subtypes of K+ channels.
In physiological condition, K+ channels mainly elicit an inhibitory modulation in central nervous system. Functional deficiency
or expressional down-regulation of K+ channels may enhance neuronal excitability, induce pathological condition, and
thus leads to CNS diseases, such as epilepsy [3]. The suppression of G protein-gated K+ (GIRK) channels are related to the
pathogenesis of Parkinson’s disease, drug addiction, cerebellar ataxia, pain and analgesia [4]. Some K+ channels can also control
the local microenvironment by regulating the extracellular K+ concentration.
This thematic issue has reviewed those research works describing the experimental discoveries, as well as the pathological
effect of K+ channels. In addition, some reviews in this thematic issue also summarized other ion channels, such as Na+ channels,
Ca2+ channels, Cl- channels, transient receptor potential cation (TRP) channels and synaptic receptors (AMPA, NMDA,
GABA receptors), concentrating on their correlationship with K+ channels and CNS diseases.
First of all, Zang K. et al. [6] and Zhu Y. et al. [7] focused on the large conductance calcium-activated K+ (BK) channels,
and retrospected the most recent scientific literature on the structure, subunits and locations of BK channels, broadly describing
the functional effects of different BK types on neurons, astrocytes, microglias, oligodendrocytes and smooth muscle cells. After
that, two reviews both concentrated on the modulation of BK channels on the epilepsy, and discussed the possibility of developing
potential antiepileptics targeted on different BK subunits. In the conclusion, the authors optimistically prospected that the
SNPs (single nucleotide polymorphisms) of KCNMA1 and KCNMBs might be the future investigation targets of BK channel
dysfunction, and optogenetic technique could be helpful to suppress the epileptic seizures [6-7].
Gao F. et al. [8] and Feng X. et al. [9] more specifically evaluated recent research papers on particular K+ channels. Gao et
al. reviewed those K+ channels in Müller glial cells, which located on the retina and related to the retinal disorders, including
retinal ischemia-reperfusion, diabetic retinopathy, inherited retinal dystrophy, retinal detachment, proliferative vitreoretinopathy
and glaucoma. These retinal K+ channels, such as BK channel, delayed rectifier K+ channel (KDR) and A-type K+ channel,
keep the hyperpolarized potential and contribute to retinal neuronal damage in pathological conditions, which may serve as
potential targets to develop new therapeutic approaches in the future [8].
Feng et al. reviewed the functions and pathological relations of lysosomal K+ channels with neurodegenerative diseases,
which were also called lysosomal storage diseases (LSDs). Lysosomal BK channel and transmembrane protein 175
(TMEM175), a novel lysosomal K+ channel, have been reviewed in this paper, describing their structure, expression on
lysosomal plasma membrane, modulation effects on Ca2+ signaling and lipid metabolism. Dysfunction of lysosomal BK channels
and TMEM175 elicits LSD-related Fabry disease and Hunter syndrome, which can be rescued by specific K+ channel agonists
[9].
Yang J. et al. [10] reviewed the oxidation of K+ channels in neurodegenerative diseases, such as Alzheimer’s disease (AD)
and Parkinson’s disease (PD). This short review elucidated the damages of different K+ channels caused by reactive oxygen
species (ROS). Oxidation of KV2.1, KV3.4, KV4.3, BK, KATP and organellar K+ channel causes the abnormal features such as
mitochondrial dysfunction, oxidative stress and autophagy compromise, which will result in collapse of intracellular homeostasis
and eventually leads to cell death [10].
In this thematic issue, Wu X. et al. [11] and Yan R. et al. [12] reported their experimental findings on inwardly rectifying
K+ (Kir) channels, both through patch clamp electrophysiological recordings. Wu et al. affirmed that tenidap, an inhibitor of
cyclooxygenase / arachidonate 5-lipoxygenase (COX/5-LOX), served as the opener of Kir2.3 channel and possessed antiepileptic
effect in cyclothiazide induced epileptiform seizures [11]. Meanwhile, Yan et al. reported that Jingshu Keli, a herbal formula
of traditional Chinese medicine (TCM), alleviated the mechanical and thermal symptoms of cervical spondylotic myelopathy
by increasing the phosphorylation level of Kir3.1 [12]. These two works are the only original researches in this thematic issue,
which may enhance the value and significance of this thematic issue, on contributing the advancement of knowledge in K+
channels.
Here we mention the TCMs, which represent a large group of medicinal compounds derived from plants and other natural
sources. Those studies of the effects of TCMs on different K+ channels provide new insights on the pharmacognostic aspects to
research K+ channels and CNS diseases. Recent studies have detected several compounds from TCMs that serve as novel K+
channel modulators, for example, curcumin (from Curcuma longa) as blocker to KV1.3, KV1.4, KV2.1 channels [13-15], puerarin
(from Pueraria lobata) as inhibitor to Kir2.1, Kir2.3, KV7.1 channels [16]. In the study from Yan et al., two saponins, ginsenoside
Rb1 (GRb1) and notoginsenoside R1 (NGR1), were also found that acted as an antagonist to Kir currents [12].
To further investigate the modulation of TCMs on K+ channels and other ion channels, Huang Y. et al. was then provided a
review elucidating the recent studies of TCMs and ion channel [17]. In this review, several TCM herbs and their containing
active ingredients were introduced, including Salvia miltiorrhiza Radix et Rhizoma, Ligusticum chuanxiong Rhizoma, Angelica
sinensis Radix, Panax ginseng Radix et Rhizoma, Panax notoginseng Radix et Rhizoma, Uncaria rhynchophylla Ramulus Cum
Uncis, Scutellaria baicalensis Radix and so on [17].
Finally, Zhou Y. et al. [18] and Feng Y. et al. [19] focused on the voltage-gated Na+ channels (VGSCs) and reviewed their
functional relationship to CNS diseases from recent scientific literature. Zhou et al. discussed the roles of VGSCs in the processing
of sensory information, including auditory sense, visual sense, olfactory sense, tactile sense and taste sense, as well as
related disorders caused by the dysfunction of VGSCs [18]. Meanwhile, Feng et al. retrospected the mutations of VGSC
subunits both on the aspects of genotypes and phenotypes, and introduced specific CNS diseases elicited by VGSC mutations,
especial the epilepsy. In this review, those mutations located on SCN1A (NaV1.1), SCN2A (NaV1.2), SCN3A (NaV1.3),
SCN8A (NaV1.6) and SCN9A (NaV1.7) were described [19]. These two reviews were included into this thematic issue to exhibit
the similarities and differences between Na+ channels and K+ channels, as well as their correlations, in the pathology of
CNS diseases.
We hope that this special issue represents a valuable contribution to understand the roles of different K+ channels, as well as
other ion channels, in the pathogenesis of CNS diseases like epilepsy.