Role of Heteromultimers in the Generation of Myocardial Transient Outward K ⁺ Currents

Abstract

Abstract-Previous studies have demonstrated a role for Kv4 ␣ subunits in the generation of the fast transient outward K ϩ current, I to,f , in the mammalian myocardium. The experiments here were undertaken to explore the role of homomeric/heteromeric assembly of Kv4.2 and Kv4.3 and of the Kv channel accessory subunit, KChIP2, in the generation of mouse ventricular I to,f . Western blots reveal that the expression of Kv4.2 parallels the regional heterogeneity in I to,f density, whereas Kv4.3 and KChIP2 are uniformly expressed in adult mouse ventricles. Antisense oligodeoxynucleotides (AsODNs)

IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Neuronal Firing in the Suprachiasmatic Nucleus and Circadian Rhythms in Locomotor Activity

“…The voltage-clamp experiments revealed that the loss of either Kv1.4 or Kv4.2 reduces I A density in SCN neurons by ϳ50%. Although Kv4.3 mRNA is expressed in the SCN and the Kv4.3 protein can associate and form heteromultimeric channels with Kv4.2 (Guo et al, 2002) and has been shown to encode I A channels in cortical pyramidal neurons (Norris and Nerbonne, 2010), the loss of Kv4.3 expression had no measureable effects on I A densities, electrical activity, or circadian rhythms in SCN neurons.…”

KChIPs and Kv4 α Subunits as Integral Components of A-Type Potassium Channels in Mammalian Brain

“…The very low density of Kv4.3 immunoreactivity in CA1 compared with CA3 pyramidal cells suggest that in CA1 pyramidal cells, the majority of A-type channel complexes are homomeric Kv4.2 channels. To our knowledge, there is little published data exploring the detailed biophysical properties of heteromeric channels formed by coexpression of Kv4.2 and Kv4.3 or concatenated ␣ subunits (but see Guo et al, 2002). Nevertheless, the dramatic change in Kv4 ␣ subunit expression in these adjacent hippocampal subfields is intriguing.…”

Left Ventricular Hypertrophy

“…In contrast with the global increases in transcript expression with hypertrophy, transcript expression of the I to,f channel ␣ subunits Kv4.2 (KCND2) and Kv4.3 (KCND3) 19,24 was not significantly different in TAC and sham LV, and expression of the I to,f channel accessory subunit KChIP2 (KCNIP2) 24 was actually slightly lower in TAC LV ( Figure 5C). The expression of transcripts encoding I K1 channel ␣ subunits Kir2.1 (KCNJ2) and Kir2.2 (KCNJ12), 23 and of the K2P channel subunit TASK1 (KCNK3), which has been suggested to underlie I ss in rat cardiomyocytes, 26 as well as TASK2 (KCNK5), was unaffected in TAC LV ( Figure 5C).…”

“…14,19,[22][23][24] Because accumulating evidence suggests that cardiac ion channels function as components of macromolecular complexes, 25 TaqMan low-density arrays 16 were exploited to allow quantitative determinations of multiple transcripts simultaneously. The amount of total RNA isolated from TAC LV was significantly (PϽ0.01) higher (1.7-fold on average) than from sham LV ( Figure 5A).…”