Characterization of stretch-activated ion currents in isolated atrial myocytes from human hearts.
To explore further the mechanisms that may underlie cardiac arrhythmia, we analysed stretch-activated ion currents in human atrial myocytes. Longitudinal stretch of freshly isolated atrial myocytes prolonged the duration of action potentials, depolarized the resting membrane potential and caused extra action potentials. Under voltage-clamp conditions, the amplitude of stretch-induced transmembrane currents increased reversibly with the intensity of stretch. Stretch-activated currents ( I(SAC)) had a reversal potential of 0 mV and were insensitive to substitution of Cl(-) with aspartate ions in the extracellular fluid. I(SAC) was suppressed by 5 micro M gadolinium (Gd(3+)). Furthermore, mechanical stretch decreased transmembrane ion fluxes through L-type calcium channels (I(Ca,L)). This reduction of I(Ca,L) was inhibited by dialysing the cells for 5 min with 5 mM BAPTA prior to application of stretch. In contrast, both BAPTA and removal of Ca(2+) from the extracellular bathing solution had no significant effect on stretch activation of I(SAC). These findings suggest that non-selective cation channels in human atrial myocytes are sensitive to mechanical stimulation. We propose that activation of transmembrane influx of cations, preferentially Na(+), by local stretch may play a role in cardiac arrhythmia.
Kamkin
Andre
A
Johannes-Müller-Institut für Physiologie, Humboldt-Universität, Charité, Tucholskystrasse 2, 10117 Berlin, Germany.
Kiseleva
Irina
I
Wagner
Kay-Dietrich
KD
Bohm
Jürgen
J
Theres
Heinz
H
Günther
Joachim
J
Scholz
Holger
H
D000200:Action Potentials / Q000502:physiology; D000368:Aged; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006325:Heart Atria; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D011930:Reaction Time / Q000502:physiology
D020746:Calcium Channels, L-Type; D002412:Cations; D002614:Chelating Agents; D007473:Ion Channels; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid