BK channels regulate calcium oscillations in ventricular myocytes on different substrate stiffness

Area of Science:

• Cardiovascular Biology
• Cellular Mechanotransduction
• Ion Channel Physiology

Background:

• Substrate stiffness significantly influences cell functions, including cardiomyocyte behavior.
• The precise mechanisms by which cells perceive and respond to mechanical cues from their environment are not fully understood.
• Calcium (Ca2+) oscillations play a critical role in cardiomyocyte excitation-contraction coupling and overall function.

Purpose of the Study:

• To investigate the role of substrate stiffness in regulating spontaneous calcium (Ca2+) oscillations in cardiomyocytes.
• To elucidate the underlying molecular mechanisms, particularly the involvement of ion channels, in this mechanosensitive process.
• To determine if large-conductance calcium-activated potassium (BK) channels are implicated in the response of cardiomyocyte Ca2+ oscillations to substrate stiffness.

Main Methods:

• Primary culture of chick cardiomyocytes on substrates of varying stiffness (soft vs. stiff).
• Measurement of spontaneous Ca2+ oscillation frequency and amplitude using calcium imaging techniques.
• Pharmacological blockade of large-conductance Ca2+-activated K+ (BK) channels using specific inhibitors.
• Assessment of BK channel activity in cardiomyocytes cultured on different stiffness substrates.

Main Results:

• Chick cardiomyocytes cultured on stiff substrates exhibited significantly greater frequency and amplitude of spontaneous Ca2+ oscillations compared to those on soft substrates.
• Application of a BK channel blocker abolished the observed dependence of Ca2+ oscillations on substrate stiffness.
• BK channel activity was found to be decreased in cardiomyocytes cultured on stiff substrates.
• These findings indicate a direct link between substrate stiffness, BK channel function, and Ca2+ oscillation dynamics.

Conclusions:

• Large-conductance Ca2+-activated K+ (BK) channels are critical mediators in the regulation of Ca2+ oscillations by substrate stiffness in cardiomyocytes.
• Substrate stiffness modulates cardiomyocyte Ca2+ oscillation patterns, at least in part, through the modulation of BK channel activity.
• This study provides novel insights into the mechanosensitive properties of cardiomyocytes and highlights BK channels as key players in cellular mechanotransduction.