Date of Award

5-9-2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Gennady Cymbalyuk

Second Advisor

Vincent Rehder

Third Advisor

William Walthall

Abstract

The properties of spiking activity such as the spike shape are crucial for normal and homeostatic functioning of a neuron. For example, the spike width determines the calcium influx and correspondingly the intracellular calcium concentration ([Ca2+]i), which plays key roles in variety of cellular processes from basic neurotransmitter release to gene transcription. Dantrolene, a specific inhibitor of ryanodine channel-mediated calcium release from intracellular calcium stores, inhibits two main ionic currents in B5 neurons of mollusk Helisoma trivolvis, persistent sodium current and hyperpolarization-activated current (h-current). We developed a model of the neuronal activity of B5 neuron and investigated how the parameters of persistent sodium current (INaP) and h-current (IH) affect the spike shape. In the model of B5 neuron, either removal of IHby shifting its voltage of half-activation to more hyperpolarized values or removal of INaP by reducing its maximal conductance decreases the spike width and shifts the minimum after-hyperpolarization potential (mAHP) towards more negative values. We showed in the model that the spike width linearly correlated with calcium influx into the cell. In this model, the spike width is controlled by the inactivation variables of fast sodium, persistent sodium, and calcium currents at the spike threshold. The activation of the h-current governs membrane potential during the inter-spike interval (ISI) and determines the values of these inactivation variables. At mAHP of spike, the activation of the h-current was the only variable that substantially affected the spike width and mAHP. In conclusion, removal of the h-current or the persistent sodium current reproduced the dantrolene effects on spike shape and reduced the calcium influx through membrane calcium channels. The inactivation variables of inward currents, modulated by activation of the h-current, describe the mechanism governing the spike width.

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