Voltage-dependent modulation of L-type calcium currents by intracellular magnesium in rat ventricular myocytes |
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Authors: | Wang Min Berlin Joshua R |
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Institution: | Department of Pharmacology and Physiology, New Jersey Medical School, The University of Medicine and Dentistry of New Jersey, Newark, NJ 07101-1709, USA. |
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Abstract: | 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). |
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Keywords: | Barium current Calcium current Inactivation Tail current Voltage clamp |
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