Butera, Rinzel, Smith, 1999

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

Inhalation and exhalation movements associated with respiration in mammals are generated by networks of neurons in the lower brain stem that produce a rhythmic pattern of electrical activity. The principal neuronal kernel for rhythm generation has been located in the pre-Botzinger complex, a subregion of the ventro-lateral medulla. In order to understand respiratory rhythm generation, it is necessary to consider mechanisms incorporating intrinsic cellular pacemaker properties. These mechanisms are captured by a hybrid pacemaker model (Smith 1997; Smith et al. 1995), in which a rhythm arises from the dynamic interactions of both intrinsic and synaptic properties within a bilaterally distributed population of coupled bursting pacemaker neurons. ("Bursting" refers to a complicated pattern of electrical activity. Bursts of action potential spikes (the "active" phase) are observed, separated by a "silent" phase of membrane repolarisation).

In their 1999 paper, Robert J. Butera, J_R., John Rinzel and Jeffrey C. Smith present two computational versions of this hybrid pacemaker-network model (see and below). In the first model, bursting arises via fast activation and slow inactivation of a persistent Na⁺ current, I_NaP. In the second model, bursting arises via a fast-activating persistent Na⁺ current, I_NaP,(the inactivation term "h" has been removed) and slow activation of a K⁺ current, I_KS. In both models, action potentials are generated via fast Na⁺ and K⁺ currents. Both models are consistent with experimental data, and the authors suggest several experimental tests to demonstrate the validity of either model and to differentiate between the two mechanisms.

The complete original paper reference is cited below:

Models of Respiratory Rhythm Generation in the Pre-Bötzinger Complex. I. Bursting Pacemaker Neurons, Robert J. Butera, Jr., John Rinzel and Jeffrey C. Smith, 1999, Journal of Neurophysiology , 81, 382-397. (Full text and PDF versions of the article are available for Journal Members on the JN website.) PubMed ID: 10400966

The raw CellML description of the model can be downloaded in various formats as described in

The first mathematical model is based on a single-compartment Hodgkin-Huxley type formalism. It is composed of five ionic currents across the plasma membrane: a fast sodium current, I_Na; a delayed rectifier potassium current, I_K; a persistent sodium current, I_NaP; a passive leakage current, I_L; and a tonic current, I_{tonic_e} (although this last current is considered to be inactive in these models).

The second model appears identical to the first except with the addition of a slow K⁺ current, I_KS. (The removal of the inactivation term "h" from I_NaP is not visible in the model diagram.)