Voltage-dependent modulation of L-type calcium currents by intracellular magnesium in rat ventricular myocytes.
Effects of changing cytosolic free Mg(2+) concentration on L-type Ca(2+) (I(Ca)) and Ba(2+) currents (I(Ba)) were investigated in rat ventricular myocytes voltage-clamped with pipettes containing 0.2 or 1.8mM [Mg(2+)] ([Mg(2+)](p)) buffered with 30mM citrate and 10mM ATP. Increasing [Mg(2+)](p) from 0.2 to 1.8mM reduced current amplitude and accelerated its decay under a variety of experimental conditions. To investigate the mechanism for these effects, steady-state and instantaneous current-voltage relationships were studied with two-pulse and tail current (I(T)) protocols, respectively. Increasing [Mg(2+)](p) shifted the V(M) for half inactivation by -20mV but dramatically decreased I(Ca) amplitude at all potentials tested, consistent with a change in gating kinetics that decreases channel availability. This conclusion was supported by analysis of I(T) amplitude, but these latter experiments also suggested that, in the millimolar concentration range, [Mg(2+)](p) might also inhibit permeation through open Ca(2+) channels at positive V(M).
Wang
Min
M
Department of Pharmacology and Physiology, New Jersey Medical School, The University of Medicine and Dentistry of New Jersey, Newark, NJ 07101-1709, USA.
Berlin
Joshua R
JR
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D015640:Ion Channel Gating; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D020746:Calcium Channels, L-Type; D008274:Magnesium