Delayed activation of the cardiac pacemaker current and its dependence on conditioning pre-hyperpolarizations

The activation time course of the pacemaker current if in Purkinje fibres during hyperpolarizations is s-shaped, which requires kinetics more complex than first order. Large, short hyperpolarizations preceding a fixed activating test pulse cause the current trace to shift to the left on the time-axis, as if a delay in if activation were removed, and eventually lead to a current trace which is a simple exponential and activates with no delay during a test pulse. Current traces before and after a relatively short and small prepulse will superimpose after a time translation. Further increasing prepulse amplitude and/or duration gives current traces that cannot be made to superimpose with the test current trace. The channel opening can be described by first order kinetics only if a delay in current activation is introduced.