Figure 10.

The evolution of [Ca²⁺]_i and D throughout and between bursts and the corresponding upmodulation and downmodulation of I_K,leak (shown schematically). The cycle starts from top left and moves clockwise, and the activation of the DAP, or plateau, at any time is denoted by the circle. Threshold denotes the calcium threshold for triggering the plateau potential and not spike threshold, and depends on spike frequency. Note that the function f denotes the modulation, and not the activation, of I_K,leak. f therefore starts at zero but can go negative if [Ca²⁺]_i decays while it is still right-shifted. This negative modulation corresponds to an upmodulation of I_K,leak and leads to a hyperpolarization of the membrane potential. The sequence of events is as follows: (1) spike-driven Ca²⁺ influx depolarizes the cell by depressing I_K,leak. The depolarization triggers more spikes, further increasing [Ca²⁺]_i and so sustaining a plateau and initiating a burst; (2) subsequent spikes cause further influx and so saturate the inhibition of I_K,leak; (3) D starts to increase, desensitizing I_K,leak to Ca²⁺ and raising the plateau threshold until it is no longer self-sustaining. The plateau then collapses, and the burst terminates; (4) D decays more slowly than Ca²⁺ and so remains elevated while Ca²⁺ decays. Thus I_K,leak remains transiently desensitized, causing f to go negative and temporarily hyperpolarizing the membrane. Hyperpolarization decays as D is cleared, and becomes manifest as a slow depolarization. As both [Ca²⁺]_i and D decay, the cell returns to its initial state.