Role of If (Funny Current) on Biological Pacemaker - Insight From A Ventricular Model

Biological pacemaker has been proposed as a promising alternative to electrical pacemaker for treating patients with impaired native cardiac pacemaker. It has been verified that overexpressing the hyperpolarization-activated funny channel current (funny current, If) can induce automatic pacing activities in ventricular myocytes (VMs). In this study, possible roles of If expression in generating automaticity in VMs are systematically investigated. We implemented a computational approach to study mechanism by which increase of If induces automaticity in VMs. The TP06 model of the electrical action potential in the human VMs was modified by incorporating If formulation. When the channel conductance of If was greater than 0.09 nS/pF, the VMs showed spontaneous pacing activities. During the time course of spontaneous action potentials, incorporating If induced changes in the intracellular ionic concentrations, leading to accumulation of intracellular calcium ([Ca
²⁺
]i) as well as sodium concentration ([Na
⁺
]i), but a decrease in the intracellular potassium concentration ([K
⁺
]i). By clamping [Na
⁺
]i and [K
⁺
]i to a constant level, a fast and stable spontaneous pacemaking activity was observed. This study helps to understand the mechanism of creating biological pacemakers using If overexpression.