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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
VOLTAGE-GATED SODIUM CHANNEL NAV1.6 IS REQUIRED FOR STIMULUS EVOKED REPETITIVE ACTION POTENTIAL FIRING IN RESPONSE TO COOLING AND OXALIPLATIN IN PERIPHERAL MYELINATED AXONS
Abstract number: P139
Carr1 *R., Sittl1,2 R., Lampert1,2,3 A., Link1,2,3 A., Fleckenstein1,2,3 J., Grafe1,2,3 P.
1Heidelberg University, Department of Anaesthesiology, Medical Faculty Mannheim, Mannheim, Germany
2Ludwig-Maximilians University, Institute of Physiology, Munich, Germany
3Friedrich-Alexander University, Institute of Physiology and Pathophysiology, Erlangen, Germany
Clinical use of the chemotherapeutic agent oxaliplatin is associated with both an acute and a chronic peripheral neuropathy. The acute neuropathy develops in 8090% of patients with manifest muscle cramps and sensory paraesthesias that are triggered or exacerbated by cooling. The symptoms derive from a peripheral site of action, although the underlying mechanism has remained elusive. Using isolated segments of human and mouse nerve oxaliplatin (10100mM) induces after-potentials in the compound action potential response of myelinated axons to brief electrical stimulation (10mA, 0.1ms). The magnitude and extent of the after-activity are increased substantially by cooling. Recordings of compound and single fibre action potentials from med mice that lack functional NaV1.6 are not affected by oxaliplatin (100mM) nor cooling to 20°C. Using quantitative PCR no change in the NaV1.6 expression was seen following acute (up to 120mins.) treatment with oxaliplatin. The induction of repetitive discharge by oxaliplatin (10100mM) is thus restricted to myelinated A-fibres and dependent upon NaV1.6. The exacerbation of this effect by cooling resembles the symptoms of acute oxaliplatin neuropathy reported by patients and suggests that NaV1.6 is a requisite component.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :P139