カルシウムおよび膜電位シグナル測定による心筋細胞の興奮収縮連関異常と伝導異常の検出

抄録

Ca²⁺ overloading of cardiac muscle leads to abnormal E-C coupling such as a delayed onset of Ca²⁺ transient and an alternating occurrence of Ca²⁺ transient at electrical stimulation. In this study, we determined membrane potential signals as well as Ca²⁺ signals at the cellular level in cardiac muscles to examine a possible involvement of altered membrane excitability in this abnormal E-C coupling. Papillary muscles were dissected from guinea pig ventricles and loaded with rhod-2 and/or Di-4-ANEPPS. Muscles were field stimulated and sequential two-dimensional images of cells were acquired from an area of 0.3x0.15mm² every 8–40 ms using a laser-scanning confocal microscope. Under control condition, action potential signals were regular and simultaneous in all cells in the field of view. To induce abnormal Ca²⁺ signals, muscles were prestimulated at 2–3 Hz under hypoxic condition. In muscles showing alternating Ca²⁺ transients, action potentials were usually regular, showing no alternation. In cells showing delayed Ca²⁺ transients, onset of action potentials also delayed. Similar delayed action potentials were also observed in the presence of heptanol. These delayed onsets of action potentials can be interpreted by impaired gap junctions. In summary, there are two underlying causes for abnormal Ca²⁺ transients in Ca²⁺ overloaded heart muscles; an abnormal E-C coupling and an abnormal action potential propagation/generation. [J Physiol Sci. 2008;58 Suppl:S178]