The MinK Potassium Channel Exists in Functional and Nonfunctional Forms When Expressed in the Plasma Membrane of \u3cem\u3eXenopus\u3c/em\u3e Oocytes

The minK protein induces a slowly activating voltage-dependent potassium current when expressed in Xenopus oocytes. In order to measure the levels of minK protein in the plasma membrane, we have modified the minK gene by inserting a 9 amino acid epitope into the N- terminal domain of the protein sequence. When intact live oocytes are injected with the modified minK RNA and subsequently incubated with an antibody to this epitope, specific binding is detected, indicating that the N-terminal domain is extracellular. We found that when oocytes are injected with amounts of minK mRNA up to 50 ng, the levels of protein at the surface are proportional to the amount of injected mRNA. In contrast, the amplitude of the minK current recorded in the oocytes saturates at 1 ng of injected mRNA. Although the amplitude of the currents is not altered by increasing mRNA levels above 1 ng, the kinetics of activation of the current differ in oocytes with high or low levels of minK RNA. In particular, activation is slower with higher levels of minK protein in the plasma membrane. Finally, we find that increasing intracellular cAMP levels, which increases the amplitude of minK currents, does not alter surface expression of the minK protein but produces a small increase in the rate of activation of the current. Our results support a model in which minK protein forms functional potassium channels by association with a factor endogenous to the oocyte

Modulation by cAMP of a Slowly Activating Potassium Channel Expressed in \u3cem\u3eXenopus\u3c/em\u3e Oocytes

When expressed in the Xenopus oocyte, the minK protein induces a slowly activating voltage-dependent potassium current (Isk). We studied the modulation of this current by altering intracellular cAMP levels and found that the amplitude of Isk is dramatically increased by treatments that raise cAMP levels and decreased by agents that lower cAMP levels. Preinjection of a protein inhibitor of the cAMP-dependent protein kinase blocked the effects of increased cAMP levels. There were no changes in the voltage dependence or kinetics of Isk. Mutations that eliminate a potential phosphorylation site on the minK protein did not block the effects of activating the kinase. In addition, the membrane capacitance of the oocyte increased and decreased in parallel with Isk. Our results fit a mechanism in which channel proteins are selectively inserted into and removed from the plasma membrane in response to changes in kinase activity

Emerging role of the KCNT1 Slack channel in intellectual disability

The sodium-activated potassium KNa channels Slack and Slick are encoded by KCNT1 and KCNT2, respectively. These channels are found in neurons throughout the brain, and are responsible for a delayed outward current termed IKNa. These currents integrate into shaping neuronal excitability, as well as adaptation in response to maintained stimulation. Abnormal Slack channel activity may play a role in Fragile X syndrome, the most common cause for intellectual disability and inherited autism. Slack channels interact directly with the Fragile X Mental Retardation protein (FMRP) and IKNa is reduced in animal models of Fragile X syndrome that lack FMRP. Human Slack mutations that alter channel activity can also lead to intellectual disability, as has been found for several childhood epileptic disorders. Ongoing research is elucidating the relationship between mutant Slack channel activity, development of early onset epilepsies and intellectual impairment. This review describes the emerging role of Slack channels in intellectual disability, coupled with an overview of the physiological role of neuronal IKNa currents

Calcium- and sodium-activated potassium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Calcium- and sodium- activated potassium channels are members of the 6TM family of K channels which comprises the voltage-gated KV subfamilies, including the KCNQ subfamily, the EAG subfamily (which includes herg channels), the Ca2+-activated Slo subfamily (actually with 6 or 7TM) and the Ca2+- and Na+-activated SK subfamily (nomenclature as agreed by the NC-IUPHAR Subcommittee on Calcium- and sodium-activated potassium channels [124]). As for the 2TM family, the pore-forming a subunits form tetramers and heteromeric channels may be formed within subfamilies (e.g. KV1.1 with KV1.2; KCNQ2 with KCNQ3)

Calcium- and sodium-activated potassium channels (KCa, KNa) in GtoPdb v.2023.1

Calcium- and sodium- activated potassium channels are members of the 6TM family of K channels which comprises the voltage-gated KV subfamilies, including the KCNQ subfamily, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 6 or 7TM) and the Ca2+- and Na+-activated SK subfamily (nomenclature as agreed by the NC-IUPHAR Subcommittee on Calcium- and sodium-activated potassium channels [126]). As for the 2TM family, the pore-forming a subunits form tetramers and heteromeric channels may be formed within subfamilies (e.g. KV1.1 with KV1.2; KCNQ2 with KCNQ3)

Calcium- and sodium-activated potassium channels (KCa, KNa) in GtoPdb v.2021.3

Calcium- and sodium- activated potassium channels are members of the 6TM family of K channels which comprises the voltage-gated KV subfamilies, including the KCNQ subfamily, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 6 or 7TM) and the Ca2+- and Na+-activated SK subfamily (nomenclature as agreed by the NC-IUPHAR Subcommittee on Calcium- and sodium-activated potassium channels [125]). As for the 2TM family, the pore-forming a subunits form tetramers and heteromeric channels may be formed within subfamilies (e.g. KV1.1 with KV1.2; KCNQ2 with KCNQ3)

Functional Analysis of a Novel Potassium Channel (KCNA1) Mutation in Hereditary Mokymia

Myokymia is characterized by spontaneous, involuntary muscle fiber group contraction visible as vermiform movement of the overlying skin. Myokymia with episodic ataxia is a rare, autosomal dominant trait caused by mutations in KCNA1, encoding a voltage-gated potassium channel. In the present study, we report a family with four members affected with myokymia. Additional clinical features included motor delay initially diagnosed as cerebral palsy, worsening with febrile illness, persistent extensor plantar reflex, and absence of epilepsy or episodic ataxia. Mutation analysis revealed a novel c.676C>A substitution in the potassium channel gene KCNA1, resulting in a T226K nonconservative missense mutation in the Kv1.1 subunit in all affected individuals. Electrophysiological studies of the mutant channel expressed in Xenopus oocytes indicated a loss of function. Co-expression of WT and mutant cRNAs significantly reduced whole-oocyte current compared to expression of WT Kv1.1 alone