Functional roles of ionic currents in a membrane delimited mouse sino-atrial node model
Kharche S., Higham J., Lei M., Zhang H.
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 (Ist) and sodium currents ( INa,1.1, INa,1.5) had no effect. Blocking the L-type calcium current's Cav1.3 isoform (ICaL1.3) and rapidly activating delayed rectifier arrested pacemaking. Blocking sodiumcalcium exchanger (I NaCa) caused a CL reduction but did not affect DDR. Reducing [Ca 2+]i increased CL marginally. A small increase of [Ca 2+]i arrestedpacemaking. Ist, I Na1.1, and INa1.5are not functional and INaCa is a background current in the model.