Suchergebnisse

K+ channels play critical roles in the proliferation and activation of lymphocytes. Mouse B cells express large-conductance background K+ channel (LK bg) in addition to the voltage-gated K+ channel (Kv) and Ca2+-activated K+ channel current (IKCa1). Mibefradil, a blocker of T-type Ca2+ channels, has been reported to affect the proliferation of immune cells. In this study, we investigated the effects of mibefradil on the membrane potential and ion channels in murine B cell lines, WEHI-231 and Bal-17. In the whole-cell patch clamp experiments, mibefradil blocked Kv and LK bg current with half inhibitory concentration (IC50), 1.9 and 2.3 microM, respectively. Interestingly, IKCa1 current was increased by mibefradil. In the inside-out patch clamp study with cloned murine IKCa1 (mIKCa1) in HEK-293, mibefradil increased both Ca2+ sensitivity and maximum activity of mIKCa1. At high concentrations (>10 microM), mibefradil inhibited mIKCa1 in a voltage-dependent manner. Application of anti-IgM antibody to stimulate B cell receptors (BCR-ligation) induced transient hyperpolarization of Bal-17 and WEHI-231 cells, which became persistent with 1 microM mibefradil. The hyperpolarizing response was abolished by charybdotoxin, a selective blocker for SK4/IKCa1. In summary, our study firstly reports the ion channel-activating effects of mibefradil. The selective potent activation of IKCa1 suggests that mibefradil-derived drugs might be useful in the control of cell responses related with IKCa1. ; This work was supported by the Korea Research Foundation Grant funded by the Korean Government (Ministry of Education and Human Resources Development) (KRF-2005-041- E00019).

EPDF and EPUB available Open Access under CC-BY-NC-ND licence. Groups most severely affected by COVID-19 have tended to be those marginalised before the pandemic and are now being largely ignored in developing responses to it. This two-volume set of Rapid Responses explores the urgent need to put co-production and participatory approaches at the heart of responses to the pandemic and demonstrates how policymakers, health and social care practitioners, patients, service users, carers and public contributors can make this happen. The second volume focuses on methods and means of co-producing during a pandemic. It explores a variety of case studies from across the global North and South and addresses the practical considerations of co-producing knowledge both now - at a distance - and in the future when the pandemic is over