TY - JOUR

T1 - Cell volume and membrane stretch independently control K+ channel activity

AU - Bomholtz, Sofia Hammami

AU - Willumsen, Niels J

AU - Olsen, Hervør L

AU - Morera, Francisco J

AU - Latorre, Ramón

AU - Klaerke, Dan A

N1 - Keywords: Animals; Cell Line; Cell Membrane; Cell Size; Electric Stimulation; Electrophysiological Phenomena; Female; Humans; Hydrostatic Pressure; Hypertonic Solutions; Isotonic Solutions; KCNQ Potassium Channels; Large-Conductance Calcium-Activated Potassium Channel beta Subunits; Large-Conductance Calcium-Activated Potassium Channels; Mechanotransduction, Cellular; Membrane Potentials; Oocytes; Potassium Channels; Transfection; Xenopus laevis

PY - 2009

Y1 - 2009

N2 - A number of potassium channels including members of the KCNQ family and the Ca(2+) activated IK and SK, but not BK, are strongly and reversibly regulated by small changes in cell volume. It has been argued that this general regulation is mediated through sensitivity to changes in membrane stretch. To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (approximately 50 microm(2) macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK current increases with increasing negative hydrostatic pressure (suction) applied to the pipette. Thus, at a pipette pressure of -5.0 +/- 0.1 mmHg the increase amounted to 381 +/- 146% (mean +/- S.E.M., n = 6, P < 0.025). In contrast, in oocytes expressing the strongly volume-sensitive KCNQ1 channel, the current was not affected by membrane stretch. The results indicate that (1) activation of BK channels by local membrane stretch is not mimicked by membrane stress induced by cell swelling, and (2) activation of KCNQ1 channels by cell volume increase is not mediated by local tension in the cell membrane. We conclude that stretch and volume sensitivity can be considered two independent regulatory mechanisms.

AB - A number of potassium channels including members of the KCNQ family and the Ca(2+) activated IK and SK, but not BK, are strongly and reversibly regulated by small changes in cell volume. It has been argued that this general regulation is mediated through sensitivity to changes in membrane stretch. To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (approximately 50 microm(2) macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK current increases with increasing negative hydrostatic pressure (suction) applied to the pipette. Thus, at a pipette pressure of -5.0 +/- 0.1 mmHg the increase amounted to 381 +/- 146% (mean +/- S.E.M., n = 6, P < 0.025). In contrast, in oocytes expressing the strongly volume-sensitive KCNQ1 channel, the current was not affected by membrane stretch. The results indicate that (1) activation of BK channels by local membrane stretch is not mimicked by membrane stress induced by cell swelling, and (2) activation of KCNQ1 channels by cell volume increase is not mediated by local tension in the cell membrane. We conclude that stretch and volume sensitivity can be considered two independent regulatory mechanisms.

U2 - 10.1113/jphysiol.2008.163550

DO - 10.1113/jphysiol.2008.163550

M3 - Journal article

C2 - 19289549

VL - 587

SP - 2225

EP - 2231

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - Pt 10

ER -