Pharmacology of the human red cell voltage-dependent cation channel. Part II: inactivation and blocking.
Pharmacological modulation of the nonselective voltage-dependent cation (NSVDC) channel from human erythrocytes was studied. Using the inorganic cations ruthenium red and La3+, as well as the organic thiol group reagents iodoacetamide (IAA) and N-ethylmaleimide (NEM), it was possible to demonstrate a concentration-dependent decrease in the voltage-activated conductance, reflecting an inhibition or inactivation of the channel. Initial voltage activation was achieved by injecting human red cells into sucrose-substituted Ringers with a low chloride concentration, which causes a strongly positive membrane potential to develop, initially determined by the equilibrium potential for Cl- ( approximately +100 mV). Due to the voltage- and time-dependent activation of the cation channel, net effluxes, minimized by addition of a chloride conductance blocker, occurred and Vm gradually decreased and stabilized at a value less positive than E(Cl), reflecting the increased cation conductance, g+, reaching 1.5-2.0 microS/cm2. In the presence of inhibitors of the NSVDC channel, both the membrane potential repolarization and the cation efflux were diminished.
Bennekou
Poul
P
The August Krogh Institute, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark. pbennekou@aki.ku.dk
Barksmann
Trine L
TL
Kristensen
Berit I
BI
Jensen
Lars R
LR
Christophersen
Palle
P
D002412:Cations / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000502:physiology*; D005033:Ethylmaleimide / Q000494:pharmacology*; D006801:Humans; D007460:Iodoacetamide / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D012430:Ruthenium Red / Q000494:pharmacology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D002412:Cations; D004396:Coloring Agents; D007473:Ion Channels; D013439:Sulfhydryl Reagents; D012430:Ruthenium Red; D007811:Lanthanum; D005033:Ethylmaleimide; D007460:Iodoacetamide