Osmosensitive properties of rapid and slow delayed rectifier K+ currents in guinea-pig heart cells.
1. Changes in cell volume affect a variety of sarcolemmal transport processes in the heart. To study whether osmotically induced cell volume shrinkage has functional consequences for K+ channel activity, guinea-pig cardiac preparations were superfused with hyperosmotic Tyrode's solution (1.2-2-fold normal osmolality). Membrane currents and cell surface dimensions were measured from whole-cell patch-clamped ventricular myocytes and membrane potentials were recorded from isolated ventricular muscles and non-patched myocytes. 2. Hyperosmotic treatment of myocytes quickly (< 3 min to steady state) shrank cell volume (approximately 20% reduction in 1.5-fold hyperosmotic solution) and depressed the delayed rectifier K+ current (IK). Analysis using different activation protocols and a selective inhibitor (5 micro mol/L E4031) indicated that the IK inhibition was due to osmolality and cell volume-dependent changes in the two subtypes of the classical cardiac IK (rapidly activating IKr and slowly activating IKs); 1.5-fold hyperosmotic treatment depressed the amplitudes of IKr and IKs by approximately 30 and 50%, respectively. 3. Superfusion of muscles and myocytes with 1.5-fold hyperosmotic solution lengthened the action potentials by 14-17%. Hyperosmotic treatment also caused 6-7 mV hyperpolarization that is most likely due to a concentrating of intracellular K+. 4. The inhibition of IK helps explain the lengthening of action potentials observed in osmotically stressed heart cells. These results, together with the reported IK stimulation by hyposmotic cell swelling, provide further support for cell volume-sensitive properties of cardiac electrical activity.
Ogura
Toshitsugu
T
Second Department of Physiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa-ken 920-0293, Japan. physiol2@kanazawa-med.ac.jp
Matsuda
Hiroyuki
H
Shibamoto
Toshishige
T
Imanishi
Sunao
S
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D006168:Guinea Pigs; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
D006982:Hypertonic Solutions; D015221:Potassium Channels; D011188:Potassium