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Voltage-clamp analysis and computational model of dopaminergic neurons from mouse retina

  • JIANGUO XIAO (a1), YIDAO CAI (a1), JASPER YEN (a1), MICHAEL STEFFEN (a1), DOUGLAS A. BAXTER (a1), ANDREAS FEIGENSPAN (a2) and DAVID MARSHAK (a1)...

Abstract

Isolated dopaminergic amacrine (DA) cells in mouse retina fire rhythmic, spontaneous action potentials and respond to depolarizing current with trains of low-frequency action potentials. To investigate the roles of voltage-gated ion channels in these processes, the transient A-type K+ current (IK,A) and Ca2+ current (ICa) in isolated mouse DA cells were analyzed by voltage clamp. The IK,A activated at −60 mV and inactivated rapidly. ICa activated at around −30 mV and reached a peak at 10 mV without apparent inactivation. We also extended our previous computational model of the mouse DA cell to include the new electrophysiological data. The model consisted of a membrane capacitance in parallel with eight currents: Na+ transient (INa,T), Na+ persistent (INa,P), delayed rectifier potassium (IKdr), IK,A, calcium-dependent potassium (IK,Ca), L-type Ca2+ ICa, hyperpolarization-activated cation current (Ih), and a leak current (IL). Hodgkin-Huxley type equations were used to define the voltage- and time-dependent activation and inactivation. The simulations were implemented using the neurosimulator SNNAP. The model DA cell was spontaneously active from a wide range of initial membrane potentials. The spontaneous action potentials reached 35 mV at the peak and hyperpolarized to −76 mV between spikes. The spontaneous firing frequency in the model was 6 Hz. The model DA cell responded to prolonged depolarizing current injection by increasing its spiking frequency and eventually reaching a depolarization block at membrane potentials greater than −10 mV. The most important current for determining the firing rate was IK,A. When the amplitude of IK,A was decreased, the firing rate increased. ICa and IK,Ca also affected the width of action potentials but had only minor effects on the firing rate. Ih affected the firing rate slightly but did not change the waveform of the action potentials.

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Corresponding author

Address correspondence and reprint requests to: David Marshak, Department of Neurobiology and Anatomy, The University of Texas—Houston Medical School, P.O. Box 20708, Houston, TX 77225, USA. E-mail: david.w.marshak@uth.tmc.edu

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Keywords

Voltage-clamp analysis and computational model of dopaminergic neurons from mouse retina

  • JIANGUO XIAO (a1), YIDAO CAI (a1), JASPER YEN (a1), MICHAEL STEFFEN (a1), DOUGLAS A. BAXTER (a1), ANDREAS FEIGENSPAN (a2) and DAVID MARSHAK (a1)...

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