Changes in the Ca2+-activated K+ channels of the coronary artery during left ventricular hypertrophy

Area of Science:

• Cardiovascular Physiology
• Ion Channel Biology
• Smooth Muscle Cell Function

Background:

• Left ventricular hypertrophy (LVH) is associated with reduced coronary reserve.
• Impaired smooth muscle cell (SMC) function is a proposed mechanism for reduced coronary reserve in LVH.
• Alterations in Ca2+-activated K+ (KCa) channels in coronary SMCs have been hypothesized to contribute to this impairment.

Purpose of the Study:

• To investigate whether KCa channel properties are altered in coronary SMCs during LVH.
• To determine the functional consequences of these potential alterations on coronary artery function.

Main Methods:

• Patch-clamp electrophysiology to measure KCa channel currents in coronary SMCs from control and LVH models.
• Analysis of unitary current amplitude and open probability of KCa channels.
• Western blot analysis to assess KCa channel expression.
• Vascular contraction experiments to evaluate the role of KCa channels in coronary artery tone.

Main Results:

• Whole-cell KCa currents were reduced in LVH coronary SMCs compared to controls.
• Unitary current amplitude and open probability of KCa channels were significantly decreased in LVH.
• The concentration-response curve for intracellular calcium ([Ca2+]i) was shifted rightward, indicating reduced channel sensitivity to calcium.
• Inhibition of KCa channels by tetraethylammonium (TEA) was more pronounced in control cells than in LVH cells.
• Western blot showed no difference in KCa channel expression levels.
• LVH coronary arteries exhibited increased resting tension in response to high K+ and reduced responsiveness to TEA.

Conclusions:

• KCa channel function, not expression, is impaired in coronary SMCs during LVH.
• Reduced KCa channel activity contributes to altered coronary artery tone and reduced coronary reserve in LVH.
• These findings suggest a novel mechanism for impaired coronary vasodilation in LVH.