Lanthanum blocks a specific component of IK and screens membrane surface change in cardiac cells.
Delayed rectifier outward K+ current (IK) in guinea pig ventricular myocytes represents the sum of two currents: a slowly activating delayed rectifier K+ current (IK.s) and a relatively rapidly activating delayed rectifier K+ current (IK.r), which rectifies at positive potentials and is specifically blocked by the class III antiarrhythmic agent, E-4031. La3+ was previously reported to block an unidentified component of IK in these cells. We used the whole cell voltage-clamp technique on isolated myocytes and confirmed these results: we show that the current blocked by La3+ (greater than or equal to 1 microM) is IK.r. This block is not caused by La3+ displacement of surface-bound Ca2+. Thus, in the presence of either E-4031 or La3+, IK represents the activation of a single current, IK.s. La3+ (10 microM-1 mM) also caused a positive shift in the voltage dependence of the activation curve of IK.s. When we assumed that La3+ acts to bind and screen negative surface charges on the outer sarcolemmal membrane, the external surface potential of these cells (in 1.8 mM Ca2+) could be estimated to be -19 mV. A modification of the Gouy-Chapman equation was used to estimate the equilibrium constant for La3+ binding (10.7 mM-1) and the minimum spacing between the negative charges on the surface membrane (22 A).
Sanguinetti
M C
MC
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Jurkiewicz
N K
NK
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D007811:Lanthanum / Q000494:pharmacology*; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D011188:Potassium / Q000502:physiology*
D007811:Lanthanum; D011188:Potassium; D002118:Calcium