ATP-Sensitive Potassium Channel Currents in Eccentrically Hypertrophied Cardiac Myocytes of Volume-Overloaded Rats

Abstract

ATP-sensitive potassium channels (K(ATP)) protect the myocardium from hypertrophy induced by pressure-overloading. In this study, we determined the effects of these channels in volume-overloading. We compared the effects of a K(ATP) agonist and a K(ATP) antagonist on sarcolemmal transmembrane current density (pA/pF) clamped at 20 mV increments of membrane potential from -80 to +40 mV in ventricular cardiac myocytes. The basal outward potassium pA/pF in myocytes of volume-overloaded animals was significantly smaller than that in the myocytes of sham-operated controls. Treatment of the control myocytes with the K(ATP) agonist cromakalim increased pA/pF significantly. This increase was blocked by the K(ATP) antagonist glibenclamide. Treatment of the hypertrophied myocytes from volume-overloaded animals with cromakalim and in the presence and absence of glibenclamide did not change pA/pF significantly. These findings suggest that eccentrically hypertrophied cardiac myocytes from volume-overloading may be unresponsive to specific activation/inactivation of K(ATP) and that dysfunctional K(ATP) may fail to protect the myocardium from left ventricular hypertrophy associated with volume-overloading.

Figure 1

Voltage-Current Relationships in Sham-Operated Control Rats. Sarcolemmal outward potassium current (I), expressed as current density (pA/pF), in patches of ventricular myocytes from adult control rats subjected to a sham surgical operation, treatment with the ATP-sensitive potassium channel (KATP) agonist cromakalim (100 μM), and post-treatment with the KATP antagonist glibenclamide (5 μM). The membrane voltage was clamped at steps of 10 mV from −80 mV to +40 mV. Differences in pA/pF in the presence and absence of treatment with cromakalim, and post-treatment with glibenclamide were significant only at the voltages from −20 mV to +40 mV (P < 0.05).

Figure 2

Voltage-Current Relationship in Volume-Overloaded Shunted Rats. Sarcolemmal outward potassium current (I), expressed as current density (pA/pF), in patches of ventricular myocytes from adult experimental rats subjected to a surgical operation to produce shunting of blood from the aorta to the van cava. The membrane voltage was clamped at steps of 20 mV from −80 mV to +40 mV. Differences in pA/pF in the presence and absence of treatment with cromokalim and post-treatment with glibenclamide were not significant at the voltages from −20 mV to +40 mV (P < 0.05).

Figure 3

Comparison of Effects of Cromakalim and Glibenclamide. Bars represent the sarcolemmal outward potassium current density amplitude, expressed as percentages of the control values of ventricular myocytes from control, sham-operated and shunted, volume-overloaded rats, measured at the clamp voltage of +40 mV under conditions of pretreatment with cromokalim and post-treatment with glibenclamide. Asterisk (∗) indicates statistically significant difference from control and shunt at P < 0.05. Inserts are raw data recordings showing the amplitudes of outward potassium currents (I), expressed in pA, acquired at a membrane clamp voltage of +40 mV during the control condition, pretreatment with cromokalim and post-treatment with glibenclamide; left insert from a sham-operated control and right insert from a shunted volume-overloaded rat.