Cobalt Administration Causes Reduced Contractility with Parallel Increases in TRPC6 and TRPM7 Transporter Protein Expression in Adult Rat Hearts

Exposure to circulating cobalt (Co(2+)) in patients with metal-on-metal orthopaedic hip implants has been linked to cardiotoxicity but the underlying mechanism(s) remain undefined. The aim of the current study was to examine the effects of Co(2+) on the heart in vivo and specifically on cardiac fibroblasts in vitro. Adult male rats were treated with CoCl(2) (1 mg/kg) for either 7 days or 28 days. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure Co(2+) uptake into various organs of the body. Co(2+) accumulated in the heart over time with significant levels evident after only 7 days of treatment. There was no evidence of cardiac remodelling following Co(2+) treatment as assessed by heart weight:body weight and left ventricular weight:body weight. However, a decrease in fractional shortening, as measured using echocardiography, was observed after 28 days of Co(2+) treatment. This was accompanied by increased protein expression of the ion transient receptor potential (TRP) channels TRPC6 and TRPM7 as assessed by quantitative immunoblotting of whole cardiac homogenates. Uptake of Co(2+) specifically into rat cardiac fibroblasts was measured over 72 h and was shown to dramatically increase with increasing concentrations of applied CoCl(2). Expression levels of TRPC6 and TRPM7 proteins were both significantly elevated in these cells following Co(2+) treatment. In conclusion, Co(2+) rapidly accumulates to significant levels in the heart causing compromised contractility in the absence of any overt cardiac remodelling. TRPC6 and TRPM7 expression levels are significantly altered in the heart following Co(2+) treatment and this may contribute to the Co(2+)-induced cardiotoxicity observed over time.