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.
High Effectiveness in Actions of Carfilzomib on Delayed-Rectifier K+ Current and on Spontaneous Action Potentials
