Effect of Cd2+ on Kv4.2 and Kv1.4 expressed in Xenopus oocytes and on the transient outward currents in rat and rabbit ventricular myocytes

The aim of the present study was to compare the biophysical properties and Cd2+ sensitivity of Kv4.2 and Kv1.4 in Xenopus oocytes with those of native transient outward potassium currents in rat and rabbit ventricular myocytes. In Xenopus oocytes, Kv4.2 inactivated at hyperpolarized voltages (V-1/2(inact) = -58.4 +/- 0.96 mV, n = 12) and recovered from inactivation rapidly (time constant = 224 +/- 23 ms, n = 3). Cd2+ induced large (approx. 30 mV with 500 mu M Cd2+), concentration-dependent rightward shifts in Kv4.2 steady-state activation and inactivation. Kv1.4 inactivated over more depolarized voltages than Kv4.2 (V-1/2(inact) = -49.3 +/- 1.4 mV, n = 12). Recovery from inactivation of Kv1.4 was dominated by a large slow component (time constant = 9,038 +/- 1,178 ms, n = 4). Cd2+ exerted only modest effects on Kv1.4 gating, with 500 mu M Cd2+ shifting the voltage dependence of steady-state activation and inactivation by approximately 12 mV. We show that the biophysical properties and Cd2+ sensitivity of rat ventricular I-to resemble those of heterologously expressed Kv4.2. These findings support previous suggestions that Kv4.2 is an important molecular component of I-to in adult rat heart. In addition, our findings show that I-to in rabbit ventricular myocytes and Kv1.4-based currents in Xeno pus oocytes share similar biophysical properties and sensitivity to Cd2+, suggesting that Kv1.4 may underlie I-to in rabbit ventricle. However, a number of discrepancies exist between the properties of native currents and their putative molecular counterparts, suggesting that additional proteins and/or modulatory factors may also play a role in determining the biophysical and pharmacological properties of these native currents.