“…Kv1.5 b-subunits alter both voltage-dependence of activation and slow and fast inactivation components 9,10 while KChIP subunits reduce the cell surface expression of Kv1.5 channels without changing current kinetics. 11 Protein kinase A has been reported to down-regulate Kv1.5 current through phosphorylation of Kvb1.3, 12 an accessory subunit which has a profound effect on the Kv1.5 current kinetics. Several studies have revealed that protein kinase C (PKC) modify the current kinetics of Kv1.5 through phosphorylation of either Kvb1.2 13,14 or Kvb1.3.…”
“…Kv1.5 b-subunits alter both voltage-dependence of activation and slow and fast inactivation components 9,10 while KChIP subunits reduce the cell surface expression of Kv1.5 channels without changing current kinetics. 11 Protein kinase A has been reported to down-regulate Kv1.5 current through phosphorylation of Kvb1.3, 12 an accessory subunit which has a profound effect on the Kv1.5 current kinetics. Several studies have revealed that protein kinase C (PKC) modify the current kinetics of Kv1.5 through phosphorylation of either Kvb1.2 13,14 or Kvb1.3.…”
“…Kv1.5 N-terminus also has a functional interaction with the PDZ domain containing SAP97 protein, an expression regulator for Kv1.5 [7]. Moreover, the interacting protein KChIP2 that binds to the N-termini of Kv channels and modulates their surface density was recently shown to contribute to the formation of functional Kv1.5 [13].…”
Non-synonymous single nucleotide polymorphisms (SNPs) in the KCNA5/hKv1.5 gene, which encodes for a voltage-gated K+ channel responsible for the I (Kur) current in the human atria, have been recently reported. To gain further knowledge on potential influence of hKv1.5 SNPs, we searched for their presence in a specific population of 96 French-Canadians and characterized electrophysiological properties of the variants in two cell lines. The presumed promoter (-83 bp) and coding regions were sequenced. We found three heterozygous SNPs: R87Q, A251T, and P307S. Functional analysis of SNPs transfected in Chinese hamster ovary (CHO) cells showed that both R87Q and P307S diminished the inactivation amplitude (e.g., at +60 mV, amplitudes were 89+/-26, 23+/-4, and 22+/-7 pA/pF for the wild type, R87Q and P307S, respectively; n=8, 6, and 8, respectively). Inactivation was slowed with these variants (e.g., tau (fast) at +50 mV were 270+/-48, 490+/-66, and 340+/-45 ms for the wild type, R87Q, and P307S, respectively) while R87Q additionally accelerated the rate of hKv1.5 channel opening. A dominant-negative effect was observed for R87Q but not for P307S. SNPs properties were not reproduced when expressed in the HEK293 cell line, suggesting that the regulatory beta-subunit present in CHO cells (and the human heart) is essential for the SNPs effects that we have observed.
“…31 In contrast, KChIP coexpression does not affect the properties or the densities of Kv1.4-or Kv2.1-encoded K + currents, consistent with the suggestion that the modulatory effects of the KChIPs are specific for Kv4 α-subunit-encoded Kv channels. 31 More recent studies, however, suggest that the KChIPs modulate the functional cell surface expression of Kv1.5-encoded Kv channels, 38 as well as myocardial Cav channels. 39 In addition, although KChIP binding to Kv4 α-subunits is not Ca 2+ dependent, mutations in EF hand domains 2, 3, and 4 eliminate the modulatory effects of KChIP1 on Kv4-and Kv1.5-encoded Kv currents, 31,38 suggesting a role for voltage-dependent Ca 2+ entry and intracellular Ca 2+ levels in the regulation of functional cardiac (Kv4-encoded) I to,f channels, as has been demonstrated for neuronal Kv4-encoded channels.…”
Section: Inwardly Rectifying Myocardial K + Channels Also Contribute mentioning
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