Section Days abstract book 2010.indd - RUB Research School ...

LS_15
Modulation of hERG by CASQ2 may impact Etiology of
Catecholamine-induced Polymorphic Ventricular
Tachycardia (CPVT)
Katja Steinke 1,3 , Karina Eckey 1 , Ulrike Henrion 1,2 , Gloria Fuhrmann 1 , Nathalie Strutz-
Seebohm 1 , Florian Lang 2 and Guiscard Seebohm 1
1
Biochemistry I, Cation Channel Group, Ruhr-University Bochum, 44780 Bochum,
Germany.
2
Department of Physiology I, University of Tuebingen, 72074 Tuebingen, Germany.
3
Ruhr-University Research School and Graduate School of Chemistry and Biochemistry,
Ruhr-University Bochum, 44780 Bochum, Germany.
e-mail: Katja.Steinke@rub.de
The plateau phase of the ventricular action potential is the result of balanced Ca 2+ influx and
K + efflux in cardiac myocytes. The action potential is finally terminated by repolarising K +
currents. Under β-adrenergic stimulation both, the Ca 2+ influx and delayed rectifier K +
currents IK are stimulated to maintain cardiac action potential length in a certain range to
allow a tightly controlled increase in net Ca 2+ influx. The intracellular Ca 2+ level is controlled
by a Calsequestrin2 (CASQ2)-ryanodine receptor complex, which serves as the most effective
Ca 2+ store and is located in the sarcoplasmic reticulum. Here, we study the effects of CASQ2
mutations R33Q, F189L and D307H located in highly conserved regions on the functions of
cardiac potassium channels in Xenopus oocytes using two electrode voltage clamp. As a
result, CASQ2 wild type and CASQ2-mutants modulate the IKr current, based on the hERG
channel. Further, molecular dynamics simulations suggest alterations in the dynamic behavior
of the CASQ2 mutants compared to CASQ2 wild type. These in vitro data suggest a
regulatory role of CASQ2 for hERG channels which in turn may impact etiology of
Catecholamine-induced Polymorphic Ventricular Tachycardia (CPVT).