Page 12 - BRIPeBook2021

Hyperglycaemia-induced impairment of the autorrhythmicity of mouse embryonic stem cell-derived cardiomyocytes

A Menzele H Aboalgasm R Ballo A Gwanyanya
Department of Human Biology, University of Cape Town

Background Results & Discussion

Diabetes mellitus with uncontrolled Fig 1. Suppressed beating activity Fig 2. Pro-arrhythmic tendency
hyperglycaemia induces cardiac disease
associated with life-threatening 120
arrhythmias. 100 80 p=0.005, n>20

Aim of study 1 sec Beating Rate (bpm) 60 40 49 bpm * 35 bpm Baseline glucose Beating Rate (bpm)
Baseline glucose
To explore the effects of hyperglycaemia Amplitude (1 a.u) 20 Amplitude (1 a.u) 1 sec
on cardiac autorrhythmicity 0 Baseline Baseline High
glucose
glucose High glucose
glucose
Methods High glucose High glucose

Model : Mouse embryonic stem cells Fig 4. Reduced pacemaker sensitivity
(mESCs) were differentiated into Fig 3. Unchanged action potential (AP) profile Ivabradine (10µM)
colonies (embryoid bodies - EBs) of
cardiac cells. 60 p=0.5, n=8

A spontaneously Amplitude (1 a.u) Baseline glucose Reduction in beat rate (%) 40
beating embryoid 1 sec Ivabradine (10µM) 20 22% 13%
body (EB) 0 Baseline High

Experimental design : Cultured EBs in glucose glucose
baseline (25mM) vs High (50mM) High glucose
glucose
Recordings : Beating rate (Myocyter) Conclusion
Action potential (di-4 Hyperglycaemia suppressed cardiac autorrhythmicity and enhanced cellular sensitivity to pro-arrhythmic stimulation
ANEPPS fluorescence) in mESC-derived cardiac cells, possibly through modulation of pacemaking channels