Inhibition of voltage-dependent K+ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone

• Published in: The Korean journal of physiology & pharmacology Vol. 22; no. 5; pp. 597 - 605
• Main Authors: An, Jin Ryeol, Li, Hongliang, Seo, Mi Seon, Park, Won Sun
• Format: Journal Article
• Language: Korean
• Published: 대한생리학회-대한약리학회 30.09.2018; The Korean Journal of Physiology & Pharmacology Editorial Office
• Subjects: Voltage-dependent K+ channel; Smooth muscle; Propafenone; Coronary artery; Voltage-dependent $K^+$ channel
• ISSN: 1226-4512; 2093-3827

In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent $K^+$ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent $IC_{50}$ value of $5.04{\pm}1.05{\mu}M$ and a Hill coefficient of $0.78{\pm}0.06$. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of $Na^+$ channel inhibition.