ADENOVIRUS-MEDIATED EXPRESSION OF A VOLTAGE-GATED POTASSIUM CHANNEL IN-VITRO (RAT CARDIAC MYOCYTES) AND IN-VIVO (RAT-LIVER)

Excitability is governed primarily by the complement of ion channels i n the cell membrane that shape the contour of the action potential, To modify excitability by gene transfer, we created a recombinant adenov irus designed to overexpress a Drosophila Shaker potassium channel (Ad ShK). In vitro, a variety of mammalian cell types infected with AdShK demonstrated robust expression of the exogenous channel, Spontaneous a ction potentials recorded from cardiac myocytes in primary culture wer e abbreviated compared with noninfected myocytes, Intravascular infusi on of AdShK in neonatal rats induced Shaker potassium channel mRNA exp ression in the liver, and large potassium currents could be recorded f rom explanted hepatocytes, Thus, recombinant adenovirus technology has been used for in vitro and in vivo gene transfer of ion channel genes designed to modify cellular action potentials, With appropriate targe ting, such a strategy may be useful in gene therapy of arrhythmias, se izure disorders, and myotonic muscle diseases.