The quantitative investigation of the binding process of calcium blocking drugs in a sinoatrial node.

Application of existing models of sinoatrial node pacemaker activity and of channel-drug interaction allow us to reproduce action potential changes as a result of the blocking effect of drugs. Two calcium antagonistic drugs, nifedipine and mesudipine, were investigated and as a result averaged rate constants of binding and unbinding were evaluated. The procedure applied which is based on experimental results and on computer simulations, can be used as an initial step for comparison of different drugs.

Modelling of the effects of Na+ and Ca2+ ions on the generation of action potentials by rabbit heart true pacemaker cells.

A comparison of results of modelling and physiological experiments allowed to estimate in the first approximation the quantitative contribution of calcium and sodium ions to the generation of different ionic currents determining the shape of the action potential (AP). Generally, the model reproduced adequately variations in AP shape with changes in the external concentrations of Na+ and Ca2+. At the same time the model differs slightly from the experimental results. To improve the model kinetic variables of slow inward current have to be taken into account.