Determination of L-Type Calcium Current in the Primary Hypertrophied Left Ventricular Cardiomyocytes of Hypertrophy Heart Rats/HHR

Abstract

Background: The molecular mechanisms responsible for electromechanical derangements found in primary left ventricular (LV) hypertrophy have not been clearly elucidated. Of particular interest is the voltage gated L-type Ca current (ICa L) which plays crucial role in the EC-coupling. This study aimed to investigate cardiomyocyte ICa(L) in newly developed line of rats namely HHR (hypertrophy heart rat) and NHR (normal heart rat). Methods: A pure experimental study has been conducted using male HHR (n=7 rats) and NHR (n=9 rats), aged 19-25 week. Cardiomyocytes were isolated enzymatically. By using whole cell patch clamp techniques, ICa were measured and normalized (pA/pF) for cell size determined by capacitance (Cm). In Na-free superfusate, the ICa(L) of HHR (n=18 cells) and NHR (n=12 cells) obtained at holding potential (HP) -50 mV were analyzed using Student’s t-test and one-way ANOVA (repeated measures). p<0.05 values were considered significance. Results: Myocyte mean Cm of HHR slightly increased but not significantly greater than that of NHR (364.3±22.33 pF vs 300.2±27.78 pF, p=0.08). In HHR, peak Ca current density was significantly increase, i.e, at HP -50 mV, the ICa(L) evoked at test potential (TP) -10 mV were -7.74±0.86 (HHR) vs -4.68±1.09 (NHR) pA/pF, p<0.02. Conclusions: Peak Ca current density of HHR increases approximately 1.6 times that of the NHR (-7.74±0.86 vs -4.68±1.09 pA/pF). This increase is attributed primarily to L-type Ca current, best known to peak at around TP -10 mV. The dramatic increase in sarcolemmal calcium influx in the HHR provides evidence of altered EC coupling processes in primary LV hypertrophy.