Regional effects of streptozotocin-induced diabetes on shortening and calcium transport in epicardial and endocardial myocytes from rat left ventricle

Abstract

In the heart, the left ventricle pumps blood at higher pressure than the right ventricle. Within the left ventricle, the electromechanical properties of ventricular cardiac myocytes vary transmurally and this may be related to the gradients of stress and strain experienced in vivo across the ventricular wall. Diabetes is also associated with alterations in hemodynamic function. The aim of this study was to investigate shortening and Ca2+ transport in epicardial (EPI) and endocardial (ENDO) left ventricular myocytes in the streptozotocin (STZ)‐induced diabetic rat. Shortening, intracellular Ca2+ and L‐type Ca2+ current (I Ca,L) were measured by video detection, fura‐2 microfluorimetry, and whole‐cell patch clamp techniques, respectively. Time to peak (TPK) shortening was prolonged to similar extents in ENDO and EPI myocytes from STZ‐treated rats compared to ENDO and EPI myocytes from controls. Time to half (THALF) relaxation of shortening was prolonged in ENDO myocytes from STZ‐treated rats compared to ENDO controls. TPK Ca2+ transient was prolonged in ENDO myocytes from STZ‐treated rats compared to ENDO controls. THALF decay of the Ca2+ transient was prolonged in ENDO myocytes from STZ‐treated rats compared to ENDO controls. Sarcoplasmic reticulum (SR) fractional release of Ca2+ was reduced in EPI myocytes from STZ‐treated rats compared to EPI controls. IC a,L activation, inactivation, and recovery from inactivation were not significantly altered in EPI and ENDO myocytes from STZ‐treated rats or controls. Regional differences in Ca2+ transport may partly underlie differences in ventricular myocyte shortening across the wall of the healthy and the STZ‐treated rat left ventricle.

Cell shortening and calcium dynamics in epicardial and endocardial myocytes from the left ventricle of Goto‐Kakizaki type 2 diabetic rats

“…Ventricular myocytes were isolated according to modifications of previously described techniques (Smail et al., ). In brief, animals were killed using a guillotine.…”

“…Ventricular myocytes were isolated and shortening was measured according to modifications of previously described techniques (Smail et al., ). In brief, cells were superfused (3–5 ml min −1 ) with normal Tyrode solution (mmol l −1 : 140.0 NaCl, 5.0 KCl, 1.0 MgCl 2 , 10.0 glucose, 5.0 Hepes, 1.8 CaCl 2 ; adjusted to pH 7.4 with 1 M NaOH solution).…”

“…Myocyte fura‐2 ratio (intracellular Ca 2+ ) was measured in fura‐2 AM‐loaded myocytes according to previously described techniques (Smail et al., ). In brief, cells were alternately illuminated by 340 and 380 nm light using a monochromator (Cairn Research, Faversham, UK), which changed the excitation light every 2 ms.…”

“…The THALF relaxation of shortening, TPK Ca 2+ transient and THALF decay of Ca 2+ transient were prolonged in ENDO myocytes from STZ‐treated rats compared with ENDO control animals. Sarcoplasmic reticulum fractional release was also reduced in EPI myocytes in diabetic rats compared with control animals (Smail et al., ).…”

“…The rise in intracellular Ca 2+ (Ca 2+ transient) initiates and regulates cardiac muscle contraction. Several studies have shown that L‐type Ca 2+ channels are similar in rat ventricular myocytes from the ENDO compared with EPI region (Bryant et al., ; Smail et al., ; Volk & Ehmke, ). However, results on regional differences in intracellular Ca 2+ transport in rat ventricular myocytes vary.…”