Functional roles of ionic currents in a membrane delimited mouse sino-atrial node model

Functional roles of ionic currents in a membrane delimited sino-atrial node (SAN) cell model were investigated. Ionic currents were blocked and intracellular calcium ([Ca²⁺]_i) buffered to study their effects on action potential (AP) characteristics. The simulations revealed that blocking the hyperpolarization activated current and the T-type calcium current caused an increase of cycle length (CL) due to reduced diastolic depolarization rate (DDR). Blocking of sustained outward (I_st) and sodium currents (I_Na,1.1, I_Na,1.5) had no effect. Blocking the L-type calcium current´s Ca_v1.3 isoform (I_CaL1.3) and rapidly activating delayed rectifier arrested pacemaking. Blocking sodium-calcium exchanger (I_NaCa) caused a CL reduction but did not affect DDR. Reducing [Ca²⁺]_i increased CL marginally. A small increase of [Ca²⁺]_i arrested pacemaking. I_st, I_Na1.1, and I_Na1.5 are not functional and I_NaCa is a background current in the model.