Redox Reaction Modulates Transient And Persistent Sodium Current During Hypoxia In Guinea Pig Ventricular Myocytes

Redox Reaction Modulates Transient and Persistent Sodium Current during Hypoxia in Guinea Pig Ventricular MyocytesWhole-cell and cell-attached patch clamp techniques were applied on isolated guinea pig ventricular myocytes to study the possible regulatory mechanisms of redox agent on persistent and transient sodium current related to hypoxia. The results showed hypoxia 15 min increased persistent sodium current (I_Na.P) and decreased transient sodium current (I_Na.T) at the same time while 1 mmol/ L reduced glutathione (GSH) could reverse the increased I_Na.P and the decreased I_Na.T simultaneously, both persistent and transient sodium channel activities could be reversed concurrently again by application of 1 mmol/L oxidized glutathione (GSSG). Hypoxia 15 min decreased the action potential amplitude (APA) and shortened action potential duration at 90 % repolarization (APD₉₀) of ventricular papillary cells simultaneously, while 1 mmol/ GSH could reverse the decreased APA and the shortened APD₉₀ at the same time; 1 mmol/L GSSG strengthened the decrease of APA induced by hypoxia and attenuated the decurtation of APD₉₀ induced by hypoxia compared with pure hypoxia. The correlation between I_Na.P and I_Na.T and the effects of GSH and GSSG on them suggested that during hypoxia redox regulation played a tremendous part in sodium channel activity and that I_Na.P and I_Na.T might be charged by the same channel with different gating modes in guinea pig ventricular myocytes. Judging from their alterations during hypoxia and exposure to GSH and GSSG, we speculated that an interconversion might exist between I_Na.P and I_Na.T. That was when one of them was increased; the other was decreased, vice versa. Part II Haloperidol modulation of potassium channels in rat ventricular myocytesThe effects of haloperidol on voltage-dependent potassium currents in isolated adult rat ventricular myocyte were investigated using the whole cell patch-clamp technique. Haloperidol (1μM) decreased transient outward potassium current (Ito) and inward rectifier potassium current (I_K1), but had no effect on the steady-state outward potassium current (Iss). The half-decreasing concentration (EC50) of haloperidol on Ito was 4.47μM. Haloperidol slightly shifted the steady-state activation curve of Ito toward more positive potential at the V_h point, but significantly shifted the inactivation curve to more negative potential. Haloperidol shifted the curve of time-dependent recovery of Ito from the inactivation to the right and decelerated the recovery of Ito from inactivation. In addition, haloperidol also significantly change the inactivation time constants of Ito with decreasing fast time constant and increasing slow time constant. These results indicated haloperidol might modulate potassium channels directly in rat cardiac myocytes.