TY - JOUR

T1 - Proposed Dynamics of CDB3 Activation in Human Erythrocytes by Nifedipine Studied with Scanning Flow Cytometry

AU - Yastrebova, Ekaterina S.

AU - Konokhova, Anastasiya I.

AU - Strokotov, Dmitry I.

AU - Karpenko, Andrei A.

AU - Maltsev, Valeri P.

AU - Chernyshev, Andrei V.

N1 - © 2019 International Society for Advancement of Cytometry.

PY - 2019/12

Y1 - 2019/12

N2 - Nifedipine is calcium channels and pumps blocker widely used in medicine. However, mechanisms of nifedipine action in blood are not clear. In particular, the influence of nifedipine on erythrocytes is far from completely understood. In this work, applying scanning flow cytometry, we observed experimentally for the first time the dynamics behind a significant increase of HCO3 −/Cl− transmembrane exchange rate of CDB3 (main anion exchanger, AE1, Band 3, SLC4A1) of human erythrocytes in the presence of nifedipine in blood. It was found that the rate of CDB3 activation is not limited by the rate of nifedipine binding and/or Ca2+ transport. In order to explain the experimental data, we suggested a kinetic model assuming that the rate of CDB3 activation is limited by the dynamics of the balance between two intracellular processes (1) the activation of CDB3 limited by its interaction with intracellular Ca2+, and (2) the spontaneous deactivation of CDB3. Thus the use of scanning flow cytometry allowed to clarify quantitatively the molecular kinetic mechanism of nifedipine action on human erythrocytes. In particular, the efficiency (~30) and rates of activation (~0.3 min−1) and deactivation (~10−3 min−1) of CDB3 in human erythrocytes was evaluated for two donors.

AB - Nifedipine is calcium channels and pumps blocker widely used in medicine. However, mechanisms of nifedipine action in blood are not clear. In particular, the influence of nifedipine on erythrocytes is far from completely understood. In this work, applying scanning flow cytometry, we observed experimentally for the first time the dynamics behind a significant increase of HCO3 −/Cl− transmembrane exchange rate of CDB3 (main anion exchanger, AE1, Band 3, SLC4A1) of human erythrocytes in the presence of nifedipine in blood. It was found that the rate of CDB3 activation is not limited by the rate of nifedipine binding and/or Ca2+ transport. In order to explain the experimental data, we suggested a kinetic model assuming that the rate of CDB3 activation is limited by the dynamics of the balance between two intracellular processes (1) the activation of CDB3 limited by its interaction with intracellular Ca2+, and (2) the spontaneous deactivation of CDB3. Thus the use of scanning flow cytometry allowed to clarify quantitatively the molecular kinetic mechanism of nifedipine action on human erythrocytes. In particular, the efficiency (~30) and rates of activation (~0.3 min−1) and deactivation (~10−3 min−1) of CDB3 in human erythrocytes was evaluated for two donors.

KW - adalat

KW - band 3

KW - calcium ions

KW - kinetic modeling

KW - red blood cells

KW - MEMBRANES

KW - CALCIUM-CHANNEL BLOCKERS

KW - TRANSPORT

KW - KINETICS

KW - DRUGS

KW - RED-BLOOD-CELLS

KW - BINDING-SITES

KW - EXCHANGE

KW - ANTAGONISTS

KW - CHLORIDE

UR - http://www.scopus.com/inward/record.url?scp=85075390654&partnerID=8YFLogxK

U2 - 10.1002/cyto.a.23918

DO - 10.1002/cyto.a.23918

M3 - Article

C2 - 31750613

AN - SCOPUS:85075390654

VL - 95

SP - 1275

EP - 1284

JO - Cytometry. Part A : the journal of the International Society for Analytical Cytology

JF - Cytometry. Part A : the journal of the International Society for Analytical Cytology

SN - 1552-4922

IS - 12

ER -