Nitrendipine is a potent inhibitor of the Ca²⁺‐activated K⁺ channel of human erythrocytes

Abstract

Nitrendipine, a classical blocker of L‐type Ca2+ channels, is shown to be a potent inhibitor of the Ca2+‐activated K+ channel of human erythrocytes. In erythrocytes suspended in a solution with physiological Na+ and K+ concentrations and in which the channel was activated using the Ca2+ ionophore ionomycin, nitrendipene inhibited K+(80Rb+) influx with an I 50 of around 130 nM. Similar results were obtained for K+(80Rb+) efflux, and for K+(80Rb+) influx into cells suspended in a high‐K+ medium.

Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives.

“…One pathway is the volume and pH-regulated K-Cl cotransport system (3,5). Though K-Cl cotransport activity is lower in the densest SS cells than in corresponding light and middle-density fractions, activity in these densest fractions is still higher than in AA inhibited by quinine, carbocyanine dyes (9), nifedipine (10), and nitrendipine ( 11) and with greater specificity by charybdotoxin (ChTX), a 37-amino acid peptide derived from the venom of Leiurus sequestratus (12)(13)(14). None of these drugs has been brought to clinical trial in sickle cell anemia, resulting either from low inhibitory potency (of the former) or from insufficient pharmacological specificity (of the latter) with expected attendant side effects.…”

Novel Anion Dependence of Induced Cation Transport in Malaria-infected Erythrocytes

“…In 86 Rb ϩ influx experiments cells were pretreated (for Ն10 min) with 0.1 mM ouabain to inhibit the Na ϩ /K ϩ pump, 0.01-0.1 mM bumetanide to inhibit the NaKCl 2 cotransporter, and 0.01-0.02 mM nitrendipine to inhibit the Ca 2ϩ -activated K ϩ channel (Ellory et al, 1992). In choline influx experiments the use of an extracellular choline concentration of 1 mM ensured that the endogenous erythrocyte choline carrier (which * This work was supported in part by Wellcome Trust Grants 036078/ Z/92/Z/1.5 and 041182/Z/94/Z and by the Lister Institute of Preventive Medicine.…”

ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice

“…10,[17][18][19] It is also blocked by quinine, carbocyanine, nifedipine, and nitrendipine, although with low potency and/or specificity. [20][21][22][23] The human intermediate-conductance potassium channel (hIK1) was cloned in 1997 by scientists at Oregon Health Sciences University and Icagen. 19 The biophysical properties, pharmacology, and regulation of this Ca 2ϩ -activated K ϩ channel were determined to be indistinguishable from the RBC Gardos channel.…”