Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

40 years ago a single experiment upset a decade of painstaking research on the mechanisms of rhythm generation in the heart. It did so by turning a theory of pacemaker activity upside down. Instead of attributing rhythm to decaying potassium current carrying outward current, it attributed the pacemaker depolarization to the slow activation of a channel conducting sodium ions into cardiac cells. But this was no standard upset of a theory. Like the replacement of Newtonian mechanics by relativity theory, the new theory explained every minute detail of the experimental observations that had established the theory it was replacing. Computational modelling of the heart achieved one of the major successes, the complete mapping of one theory onto another without challenging the correctness of any of the experimental findings. This review details the way in which this transition occurred and draws some important lessons for modelling of biological processes today.

Original publication




Journal article


Prog Biophys Mol Biol

Publication Date



Funny current, HCN1, HCN4, Heart rhythm, Pacemaker, Sinus node