Changes in the Ca2+-Activated K+ Channels of the Coronary Artery During Left Ventricular Hypertrophy

ABSTRACT—It has been suggested that impairment of smooth muscle cell (SMC) function by alterations in the Ca-activated K (KCa) channels accounts for the reduction in coronary reserve during left ventricular hypertrophy (LVH). However, this hypothesis has not been fully investigated. The main goal of this study was to assess whether the properties of KCa channels in coronary SMCs were altered during LVH. In patch-clamp experiments, the whole-cell currents of the KCa channels were reduced during LVH. The unitary current amplitude and open probability for the KCa channels were significantly reduced in LVH patches compared with control patches. The concentration-response curve of the KCa channel to [Ca]i was shifted to the right. Inhibition of the KCa channels by tetraethylammonium (TEA) was more pronounced in LVH cells than in control cells. Western blot analysis indicated no differences in KCa channel expression between the control and LVH coronary SM membranes. In contraction experiments, the effect of high K concentration on the resting tension of the LVH coronary artery was greater than on that of the control. The effect of TEA on the resting tension of the LVH coronary artery was reduced compared with the effect on the control. Our findings imply a novel mechanism for reduced coronary reserve during LVH.