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Functional and phosphorylation‐dependent changes in the cardiac sodium channel triggered by anesthetic‐induced preconditioning
Author(s) -
Tobin Ann A,
Tampo Akihito,
Bosnjak Zeljko J,
Kwok WaiMeng
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1224-c
Subject(s) - sodium channel , isoflurane , phosphorylation , patch clamp , protein subunit , chemistry , ischemic preconditioning , anesthetic , sodium channel blocker , blot , anesthesia , pharmacology , medicine , endocrinology , sodium , electrophysiology , biochemistry , ischemia , organic chemistry , gene
Anesthetic‐induced preconditioning (APC) is a phenomenon whereby a brief exposure to volatile anesthetics protects the heart from a prolonged ischemic episode. APC is cardioprotective reducing infarct size. In contrast, its effect on cardiac rhythm has not been established. Our previous studies suggested that APC can trigger arrhythmias. Functional changes in the voltage‐gated ion channels may underlie this arrhythmogenic effect, but the consequence of APC on these channels is unknown. In the present study, we investigated the impact of APC on the cardiac sodium channel. Preconditioned (APC) Wistar rats were administered inhaled isoflurane (1 MAC) for 30 minutes followed by a 30‐minute recovery period, prior to thoracotomy and excision of the heart. Control rats (NON) were not treated with isoflurane. Patch clamp studies on isolated myocytes indicated that APC triggered a 51% increase in the sodium channel current density, compared to the control group (−8.7±0.5 pA/pF and −13.2±1.2 pA/pF, respectively; n=12,13). Western blotting showed that APC treatment did not alter the protein expression of the pore‐forming Na v 1.5 α‐subunit or the regulatory Na v 2 β‐subunit. Immunoprecipitation using a phospho‐serine antibody and subsequent immunoblotting with an Na v 1.5 α‐subunit antibody indicated that APC treatment decreased the phosphorylation of the Na v 1.5 α‐subunit. This novel finding suggests that APC triggers changes in the functional state of the cardiac sodium channel. Supported in part by NIH P01 GM066730.