Differential Modulation of I-K and I-Ca,I-L Channels in High-Fat Diet-Induced Obese Guinea Pig Atria

[EN] Obesity mechanisms that make atrial tissue vulnerable to arrhythmia are poorly understood. Voltage-dependent potassium (I-K, I-Kur, and I-K1) and L-type calcium currents (I-Ca,I- L) are electrically relevant and represent key substrates for modulation in obesity. We investigated whether electrical remodeling produced by high-fat diet (HFD) alone or in concert with acute atrial stimulation were different. Electrophysiology was used to assess atrial electrical function after short-term HFD-feeding in guinea pigs. HFD atria displayed spontaneous beats, increased I-K (I-Kr + I-Ks) and decreased I-Ca,I- L densities. Only with pacing did a reduction in I-Kur and increased I-K1 phenotype emerge, leading to a further shortening of action potential duration. Computer modeling studies further indicate that the measured changes in potassium and calcium current densities contribute prominently to shortened atrial action potential duration in human heart. 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