Beta-adrenergic modulation of heart rate: Contribution of the slow delayed rectifier K+ current (IKs)

To assess the role of the slow delayed rectifier potassium current (I_Ks) in the β-adrenergic modulation of heart rate, we experimentally determined the effect of β adrenergic stimulation on I_Ks and used the thus obtained data in computer simulations of SA nodal pacemaker activity, employing the mathematical model of a primary rabbit SA node pacemaker cell by Kurata and coworkers. Incorporation of our experimental findings into the SA nodal cell model resulted in a 12 ms decrease in cycle length. This decrease in cycle length is similar to the 13 ms decrease observed upon incorporation of our experimental data on the effect of β-adrenergic stimulation on the hyperpolarization-activated funny current´ (I_f), also known as ´pacemaker current´. We conclude that IKs is an important contributor to the β-adrenergic modulation of heart rate.