Microglial Potassium Channels: From Homeostasis to Neurodegeneration

Abstract

The growing interest in the role of microglia in the progression of many neurodegenerative diseases is developing in an ever-expedited manner, in part thanks to emergent new tools for studying the morphological and functional features of the CNS. The discovery of specific biomarkers of the microglia phenotype could find application in a wide range of human diseases, and creates opportunities for the discovery and development of tailored therapeutic interventions. Among these, recent studies highlight the pivotal role of the potassium channels in regulating microglial functions in physiological and pathological conditions such as Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis. In this review, we summarize the current knowledge of the involvement of the microglial potassium channels in several neurodegenerative diseases and their role as modulators of microglial homeostasis and dysfunction in CNS disorders.

Behavior of KCNQ Channels in Neural Plasticity and Motor Disorders

“…However, the future direction of KCNQ neural mechanosensation literature ought to focus more on the clinical and translational use of these pharmacotherapeutic options, as most of the literature used to support this review was based on animal models alone. Despite this, there is strong evidence that could support the initiation of future clinical trials, especially for auditory pathologies as well as in PD [ 14 , 80 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ], and developments for understanding the effects that antimicrobial agents have on these potassium ion channels [ 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]. Additionally, the scope of this review was on neural modulation, yet there is a growing amount of literature on the behavior of KCNQ channels in cardiac modulations as well, especially in the cellular processes involved in arrhythmia [ 26 , 27 , 28 , 29 , 139 , 140 , 141 ,…”

“…This is where the literature ought to focus in order to determine if secondary factors that are not understood in these animal models also contribute to the memory impairment (i.e., hippocampal morphology) [ 90 , 91 , 92 , 93 , 94 , 95 ]. The epileptic phenotype, in conjunction with the cognitive impairment of these genetic models, may suggest additional psychomotor exploration [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ].…”

“…While this avenue of study has proven to be a promising utilization of these K + channels in dopaminergic pathways, they are perhaps better associated with the treatment of motor disorders involving the neurotransmitter dopamine. Parkinson’s disease (PD) is a neurodegenerative disorder commonly associated with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. As a result, the loss of nigrostriatal dopamine is associated with the motor symptoms classically observed in PD, such as muscular rigidity, bradykinesia, and tremor [ 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ].…”

“…Currently, one of the primary treatment methods for PD includes the compound L-DOPA. Within 10 years of L-DOPA administration, many PD patients receiving this drug tend to become afflicted by hyperkinetic symptoms such as chorea, myoclonus, or dystonia [ 99 , 100 , 101 ]. In rat models of L-DOPA-induced dyskinesia (LID), it was found that retigabine significantly reduced the frequency of abnormal involuntary movements (AIM).…”

La excitabilidad de las células gliales

“…77 Curiosamente su expresión disminuye ante estímulos pro-inflamatorios como la exposición a LPS; 72 mientras que la IL-4 promueve su expresión en cultivos murinos. 78 Los canales KCa3.1 están implicados en eventos de migración a través de mecanismos que incluyen señalización vía AMPc / PKA y calcio; 78,79 también están asociados a la modulación del fenotipo proinflamatorio de la microglía en distintas neuropatologías. Por ejemplo, en un modelo murino de esclerosis lateral amiotrófica (ELA) se reportó que el fenotipo pro-inflamatorio microglial se atenuaba por el bloqueo farmacológico de KCa3.1 con el antagonista selectivo TRAM-34, la muerte de las neuronas motoras disminuía, mientras que la denervación muscular se retrasaba y se incrementaba la sobrevivencia.…”