Figure 3. Direct functional effects of ^PYRapelin¹³ on atrial electrophysiology.

(A) Representative murine atrial activation isochrones (ms) at baseline and following ^PYRapelin¹³ administration (20 nM) in isolated (denervated) atria paced at 90 ms intervals from the right atrial appendage (RAA) (scale bar: 200 μm). (B) Conduction velocities calculated from the left atrial appendage (LAA) of 90 ms paced atria were increased (***P < 0.0007, 2-tailed Student’s paired t test comparing before and after ^PYRapelin¹³ administration) following ^PYRapelin¹³ administration in both exercised and sedentary control mice. (C) Representative tracings and I–V relationships of INa from isolated murine left atrial (LA) myocytes before (baseline) and after ^PYRapelin¹³ (10 nM) infusion. (D) Whole-cell voltage-clamp steady-state sodium channel activation curves were determined from single-cell recordings from sedentary CD1 mice (8–10 weeks old) of cardiac sodium current (I_Na) in freshly isolated murine LA myocytes before and after treatment with ^PYRapelin¹³ (10 nM) infusion and saline (control). In contrast to saline infusion, apelin reversibly induced a hyperpolarized voltage shift (P = 0.041) in the steady-state activation curve from –40.68 ± 2.03 mV to –46.58 ± 1.69 mV. (E) I–V relationship of I_Na from LA myocytes before and after saline revealed no change in maximal conductance. By contrast, ^PYRapelin¹³ (10 nM) infusion increased (P = 0.006) maximum conductance from 0.34 ± 0.02 pS/pF to 0.41 ± 0.02 pS/pF. Data are presented as mean ± SEM. For sodium channel measures, n = 7 myocytes/3 mouse isolated atria per group. Representative data are the result of experiments being repeated 6 times.