Gadolinium as an Inhibitor of Ionic Currents in Isolated Rat Ventricular Cardiomyocytes

The whole-cell patch-clamp technique was used to examine the effect of gadolinium Gd³⁺ (a non-specific blocker of mechanically gated current I_MGCh, a component of late current I_L) on ionic currents in insolated rat ventricular cardiomyocytes alone and in combination with the blockers of L-type calcium currents (I_CaL) nifedipine (10 μM) or verapamil (1 μM). In K⁺_in/K⁺_out or Cs⁺_in/Cs⁺_out media, blockade of I_CaL produced no effect on I_L at negative potentials, but inhibited I_L at positive ones. In K⁺_in/K⁺_out medium, Gd³⁺ (5 μM) decreased the net persistent current (I_np) at -45 mV from 198.6±6.4 to 96.7±9.5 pA over 15 min. Gd³⁺ alone or in combination with I_CaL blockers shifted the reversal potential of I_L to more negative values. At negative potentials, Gd³⁺ decreased I_K1 and inward current including I_MGCh. At positive potentials, Gd³⁺ alone or in combination with I_CaL blockers decreased I_L. When applied for 15 min in Cs⁺_in/Cs⁺_out medium at -45 mV, Gd³⁺ produced no effect on net current and inward and outward components of I_L. Thus, Gd³⁺ can be viewed as a specific blocker of I_MGCh only in Cs⁺ medium.