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The effects of the hKvbeta1.2 beta subunit of the human atrium on hKv1.5 currents were analyzed in an experimental model in which the Kvbeta subunit functioned as a channel-blocking particle. The currents from the hKv1.5 delayed rectifier K+ channel in Xenopus oocytes were rapidly activated to a plateau current level during pulses to a range of potentials in the positive voltage range. Furthermore, hKvbeta1.2 confered rapid inactivation on the delayed rectifier K+ channel hKv1.5.

KChAP/Kv[Beta]1.2 interactions and their effects on cardiac Kv channel expression. Am J Physiol Cell Physiol 281: C290-C299, 2001.--KChAP and voltage-dependent [K.sup.+] (Kv) [Beta]-subunits are two different types of cytoplasmic proteins that interact with Kv channels. KChAP acts as a chaperone for Kv2.1 and Kv4.3 channels. It also binds to Kv1.x channels but, with the exception of Kv1.3, does not increase Kv1.x currents. Kv[Beta]-subunits are assembled with Kv1.x channels; they exhibit 'chaperone-like' behavior and change gating properties. In addition, KChAP and Kv[Beta]-subunits interact with each other. Here we examine the consequences of this interaction on Kv currents in Xenopus oocytes injected with different combinations of cRNAs, including Kv[Beta].2, KChAP, and either Kv1.4, Kv1.5, Kv2.1, or Kv4.3. We found that KChAP attenuated the depression of Kv1.5 currents produced by Kv[Beta]1.2, and Kv[Beta]1.2 eliminated the increase of Kv2.1 and Kv4.3 currents produced by KChAP. Both KChAP and Kv[Beta]1.2 are expressed in cardiomyocytes, where Kv1.5 and Kv2.1 produce sustained outward currents and Kv4.3 and Kv1.4 generate transient outward currents. Because they interact, either KChAP or Kv[Beta]1.2 may alter both sustained and transient cardiac Kv currents. The interaction of these two different classes of modulatory proteins may constitute a novel mechanism for regulating cardiac [K.sup.+] currents. chaperone; modulation; potassium channels; voltage-gated potassium 1.4 channel; voltage-gated potassium 1.5 channel; voltage-gated potassium 2.1 channel; voltage-gated potassium 4.3 channel

The ClotTriever Outcomes (CLOUT) Registry evaluates real-world outcomes following treatment of acute and non-acute lower extremity proximal deep vein thrombosis (DVT) with the ClotTriever System. The prospective CLOUT Registry is actively enrolling up to 500 patients with lower extremity DVT involving the femoral, common femoral, and iliac vein, or inferior vena cava (IVC), alone or in combination, at up to 50 US sites. The CLOUT Registry will provide valuable real-world outcomes following mechanical thrombectomy with the ClotTriever System, helping define future definitive studies to advance care for this underserved population. [Extracted from the article]

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The in vitro cardiac properties of dihydroartemisinin (DHA) plus piperaquine phosphate (PQP) were compared with those of other antimalarial compounds. Results with antimalarial drugs, chosen on the basis of their free therapeutic maximum concentration in plasma (C(max)), were expressed as the fold of that particular effect with respect to their C(max). The following tests were used at 37 °C: hERG (human ether-à-go-go-related gene) blockade and trafficking, rabbit heart ventricular preparations, and sodium and slow potassium ion current interference (I(Na) and I(Ks), respectively). Chloroquine, halofantrine, mefloquine, and lumefantrine were tested in the hERG studies, but only chloroquine, dofetilide, lumefantrine, and the combination of artemether-lumefantrine were used in the rabbit heart ventricular preparations, hERG trafficking studies, and I(Na) and I(Ks) analyses. A proper reference was used in each test. In hERG studies, the high 50% inhibitory concentration (IC(50)) of halofantrine, which was lower than its C(max), was confirmed. All the other compounds blocked hERG, with IC(50)s ranging from 3- to 30-fold their C(max)s. In hERG trafficking studies, the facilitative effects of chloroquine at about 30-fold its C(max) were confirmed and DHA blocked it at a concentration about 300-fold its C(max). In rabbit heart ventricular preparations, dofetilide, used as a positive control, revealed a high risk of torsades de pointes, whereas chloroquine showed a medium risk. Neither DHA-PQP nor artemether-lumefantrine displayed an in vitro signal for a significant proarrhythmic risk. Only chloroquine blocked the I(Na) ion current and did so at about 30-fold its C(max). No effect on I(Ks) was detected. In conclusion, despite significant hERG blockade, DHA-PQP and artemether-lumefantrine do not appear to induce potential torsadogenic effects in vitro, affect hERG trafficking, or block sodium and slow potassium ion currents.