Ca²⁺ Waves within Intact Rat Cardiac Trabeculae with Nonuniform Muscle Contraction

Background: In the myocardium with nonuniform contraction, Ca²⁺ waves are initiated not only by spontaneous Ca²⁺ release from the sarcoplasmic reticulum (SR), but also by dissociation of Ca²⁺ from the myofilaments. We investigated whether nonuniform contraction affects Ca²⁺ waves. Methods: Rat trabeculae were regionally exposed to a jet of solution containing 1) 10 mM Ca²⁺ (Jet_HCa) for the induction of spontaneous Ca²⁺ release from the SR, and 2) 5 mM caffeine (Jet_Caff) or 0.2 mM Ca²⁺ (Jet_LowCa) for the regional reduction of muscle contraction. Force, sarcomere length, and [Ca²⁺]i were measured (24°C, [Ca²⁺]o=2.0 mM). Results: The JetHCa caused spatially uniform contraction, while the Jet_Caff and Jet_LowCa caused nonuniform contraction. The enhancement of force by the 10% stretch increased the propagation velocity (V_prop) of Ca²⁺ waves by the Jet_HCa, Jet_Caff, and Jet_LowCa. Interestingly, after preincubation with 10 μM colchicine, this enhancement of force did not increase the V_prop by the Jet_HCa, while it did increase it by the JetCaff and Jet_LowCa. The reduction of force by 10 μmol/L blebbistatin did not change the V_prop by the Jet_HCa, while it decreased it by the Jet_Caff and Jet_LowCa irrespective of preincubation with colchicine. Conclusions: These results suggest that even with microtubule-mediated modulation, the force developed during muscle contraction modulates the V_prop in the myocardium with nonuniform contraction.