Parameters of the Model

Capacity = 350 pF (Bostock et al., 1991) Input resistance = 450 MQ

GNa (transient) = 10.4 |S (a node of 30 |im2, with 2,000 Na channels per |im2 would be expected to have a conductance around 0.9 |S [c.f., Mclntyre et al., 2002]) GNa (persistent) = 0.15 |S

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Figure 5 Numerical simulation of an ectopically active site. (A) Membrane potential and (B) simultaneous membrane current records from a space-clamped heminode/internode. A dynamic equilibrium was reached with ectopic action potentials generated at a steady 10.5 Hz. The simulation was sufficiently long to be independent of initial conditions. (A) A pacemaker potential can be clearly seen preceding each action potential. Time calibration same in (A) and (B). (C) Changing the value of EK from -83 to -82 mV (e.g., equivalent to an increase in external [K+] by 0.2 mM if internal [K+] is taken as 120 mM) causes an increase in the discharge frequency to 22.5 Hz. (D) A more detailed plot of the pacemaker current (arrow) that precedes the large regenerative inward current seen in (B) (that is truncated in the panel). The pacemaker current is small (upwards of a few 10s of pA) and provided by a low-threshold, persistent Na+ current.

GKf = 0.4 |S GKs = 0.9 |S ENa = +69 mV EK = -83 mV Eleak = 0 mV

Integration was by the Euler method, and the integration time step was 1 |is. Calculation of rate constants at 30°C assumed a Q10 of 2 for am and ßm (for both transient and persistent Na+ current), ah and ßh, an and ßn, and a Q10 of 1.5 for as and ßs. Voltage-dependent rate constants were the same as those published in Schwarz et al. (1995), except that the persistent Na+ current activation parameters am and ßm were half the value of the same parameters for the transient current (Bostock and Rothwell, 1997), and they incorporated a 20 mV voltage offset. Persistent Na+ current also did not inactivate (c.f., Bostock and Rothwell, 1997), whereas real persistent Na+ currents are subject to voltage-dependent slow inactivation (e.g., Patlak and Oritiz, 1986; Baker and Bostock, 1998).

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