Rheological action of bepridil on normal and sickle erythrocytes

Article type: Research Article

Authors: Stuart, J.^{a; b; *} | Ellory, J.C.^{a; b} | Stone, P.C.W.^{a; b}

Affiliations: [a] Department of Haematology, Medical School, University of Birmingham, Birmingham B15 2TJ, UK | [b] Department of Physiology, University of Oxford, Oxford OX1 3PT, UK

Correspondence: [*] Correspondence to: Professor J. Stuart, Birmingham.

Note: [] Accepted by: Editor M.R. Boisseau

Abstract: Bepridil is a new calcium antagonist that was found to cause swelling and stomatocytosis of normal erythrocytes by increasing passive permeability of cations across the cell membrane. At 100 µmol/l, the drug also fully inhibited the Ca2+-activated (Gardos) K+ channel. When normal and sickle erythrocytes were dehydrated by Ca2+ loading using the ionophore A23187, bepridil at 10–100 µmol/l had a significant protective effect against loss of filterability through pores of 5 µm diameter. Bepridil has the potential to prevent erythrocyte dehydration and sickling by blocking entry of Ca2+, by inhibiting loss of K+ via the Gardos channel, and by increasing passive permeability of cations from plasma.

Keywords: Rheology, Erythrocyte deformability, Sickle cell anemia

DOI: 10.3233/CH-1989-9207

Journal: Clinical Hemorheology and Microcirculation, vol. 9, no. 2, pp. 247-255, 1989