Fig. 3: Physiological characteristics of Acomys and Mus cardiomyocytes.
From: Adult spiny mice (Acomys) exhibit endogenous cardiac recovery in response to myocardial infarction
a Representative images of isolated cardiomyocytes from C57BL6-Mus and Acomys stained with di-8-ANEPPS to visualize T-tubules. T-tubule analysis shows significantly reduced T-tubule density in transverse (b) and axial directions (c) along with wider T-tubule spacing (d) in Acomys compared to Mus (C57BL6; t = 6.2, 12, and 4.4; F = 39, 141, and 19, for b–d, respectively; Mus N = 5, n = 67; Acomys N = 3, n = 23. e Acomys ventricular cardiomyocytes show organized z-discs. (i) Mononucleated CM α-actinin reveals highly organized z-disc structure (scale bar = 10 μm). (ii) expanded view of mononucleated CM in i (scale bar = 2 μm). (iii) Representative binucleated CM (scale bars = 10 μm). f Current traces (left) current-voltage relationship (right) elicited by Vtest −25 mV (left, upper) and Vtest +15 mV (left, lower) from Vhold −80 mV. g (Left) Current-voltage curves from Vhold −80 mV and −50 mV superimposed for Acomys CM exhibiting ICa,T (A) or no ICa,T. g (Left center) ICa,T expression was heterogeneous but more Acomys ventricular CMs showed ICa,T compared to rare occurrences in Mus-C57BL6 (g, right center). g (Right) Cell capacitance was not different for Acomys CM with or without ICa,T. h Cell capacitance was greater in Mus-C57BL6 compared to Acomys (t = 2.88, F = 7.9, **P < 0.01). i Maximal conductance density trended greater in Mus-C57BL6 compared to Acomys (t = 2.0, F = 7.7, P = 0.06). j–k Voltage-dependent activation and inactivation of ICa,L was significantly shifted positive for Acomys compared to Mus-C57BL6 (t = 5.8 and 5.2, F = 3.7 and 4.5, for i, j, respectively, ****P < 0.001). l Representative calcium transients from isolated ventricular cardiomyocytes loaded with fura2-AM, Mus-C57BL6 (top, red) and Acomys (bottom, blue) paced at 1 Hz. Scale bar: 2 s. l (Left) Amplitude of the transients (t = 3.7, F = 1.4, ***P = 0.0004). l (Middle) Velocity at which calcium enters the cytosol (upstroke of the transient: t = 2.1, F = 1.5, *P = 0.04). l (Right) (τ) Calcium transient decay (t = 3.6, F = 1.5, ***P = 0.0005). m Representative calcium transients treated with 100 nM isoproterenol (ISO), Mus-C57BL6 (top, red) and Acomys (bottom, blue), paced at 1 Hz. Scale bar: 2 s. (Left) Before and after ISO Amplitude of the transients (t = 2.8 for Mus, P = 0.53, t = 0.7 for Acomys, **P = 0.007). (Middle) Before and after ISO Velocity at which calcium enters the cytosol (t = 2.5, P = 0.02). (Right) Calcium transient decay (t = 3.4 for Mus, **P = 0.002; N = 7 animals, n = 37 cells for C57BL6-Mus; and N = 4 animals, n = 31 cells for Acomys).
