Biomedical Engineering and Bioengineering Commons^™

Isoform-Specific Stimulation Of Cardiac Na/K Pumps By Nanomolar Concentrations Of Glycosides., Glenn Gaudette, Junyuan Gao, Randy Wymore, Yongli Wang, Irvin Krukenkamp, Ira Cohen, Richard Mathias

Glenn R. Gaudette

It is well-known that micromolar to millimolar concentrations of cardiac glycosides inhibit Na/K pump activity, however, some early reports suggested nanomolar concentrations of these glycosides stimulate activity. These early reports were based on indirect measurements in multicellular preparations, hence, there was some uncertainty whether ion accumulation/depletion rather than pump stimulation caused the observations. Here, we utilize the whole-cell patch-clamp technique on isolated cardiac myocytes to directly measure Na/K pump current (I(P)) in conditions that minimize the possibility of ion accumulation/depletion causing the observed effects. In guinea pig ventricular myocytes, nanomolar concentrations of dihydro-ouabain (DHO) caused an outward current that appeared …