Local membrane deformations activate Ca2+-dependent K+ and anionic currents in intact human red blood cells

Area of Science:

• Biophysics
• Cell Biology
• Physiology

Background:

• Red blood cell (RBC) mechanical properties are crucial for capillary passage.
• Membrane permeability increases under shear stress and deformation, observed in conditions like sickle cell anemia.
• Previous studies relied on RBC suspensions, lacking single-cell deformation analysis.

Purpose of the Study:

• Investigate membrane currents activated by controlled, local RBC deformation.
• Characterize the nature of stretch-activated currents in single red blood cells.
• Utilize the on-cell patch clamp technique for precise measurements.

Main Methods:

• Employed the cell-attached patch-clamp configuration on intact red blood cells.
• Induced membrane deformation using brief negative pressure pulses (10 mmHg).
• Recorded single channel activity and ion currents under controlled deformation.

Main Results:

• Stretch-activated currents were detected only during membrane deformation.
• Observed Ca(2+)-dependent K(+) and Cl(-) currents.
• Identified transient, spontaneous inactivation of stretch-activated Ca(2+) permeability (PCa) with decay half-times of 5-10 min.
• Deformation led to increased intracellular Ca(2+), activating K(+) channels and anion currents.

Conclusions:

• Local membrane deformation transiently activates Ca(2+) permeability (PCa) in RBCs.
• This mechanism likely contributes to Ca(2+)-mediated effects in normal RBC aging.
• Elevated Ca(2+) content in hereditary anemias (thalassemia, sickle cell anemia) may involve this pathway.