Contribution of a slowly inactivating potassium current to the transition to firing of neostriatal spiny projection neurons

Abstract

1. Neostriatal spiny projection neurons display a prominent slowly depolarizing (ramp) potential and long latency to spike discharge in response to intracellular current pulses. The contribution of a slowly inactivating A-current (IAs) to this delayed excitation was investigated in a neostriatal slice preparation using current pulse protocols incorporating information based on the known voltage dependence, kinetics, and pharmacological properties of IAs. 2. Depolarizing intracellular current pulses evoked a slowly developing ramp potential that could last for seconds without reaching steady state and continued until either the pulse was terminated or spike threshold was reached. The slope of the ramp potential was dependent on the level of depolarization achieved by the membrane, and the apparent activation threshold for this ramp depolarization was approximately -65 mV. 3. Application of low concentrations of 4-aminopyridine (4-AP, 30-100 microM) or dendrotoxin (DTX, 30 nM), which are known to selectively block IAs, reduced both the slope of the ramp potential and the latency to first spike discharge. As has been described previously, blockade of inward Na+ and Ca2+ currents with tetrodotoxin (TTX, 1 microM) and cadmium (400 microM) also reduced the slope of the ramp depolarization. 4. A conditioning-test pulse protocol was used to examine the voltage dependence of inactivation of the ramp potential and long first spike latency. In the absence of a conditioning pulse, the test pulse evoked a slowly rising ramp potential and a spike with a long latency to discharge. A conditioning depolarization to approximately -60 mV decreased the slope of the ramp potential and the latency to first spike discharge evoked by the test pulse. A conditioning hyperpolarization to potentials below -100 mV, increased first spike latency. Application of a low concentration of 4-AP (100 microM) abolished the influence of prior membrane potential on the slope of the ramp depolarization and the latency to first spike discharge. 5. The kinetics of recovery from inactivation of the 4-AP-sensitive current were studied in the presence of TTX and cadmium by depolarizing cells to approximately -50 mV and then stepping to approximately -90 mV for increasing periods of time (0.5-5.0 s) before delivering a test pulse. The amplitude of the test pulse response decreased as a function of the hyperpolarizing step duration. When the test pulse response amplitudes were plotted against the hyperpolarizing step duration, the points reflected an exponential decay with an average time constant of 2.05 +/- 1.38 (SD) s.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationships Among Seizures, Extracellular Amino Acid Changes, and Neurodegeneration Induced by 4‐Aminopyridine in Rat Hippocampus: A Microdialysis and Electroencephalographic Study

“…Thus, it can be concluded that the 4-AP-induced EEG discharges are the result of an increment in frequency firing, combined with an increased excitatory glutamate-and GABA-mediated synaptic transmission. Consistent with this conclusion, it has been found that dendrotoxins, like 4-AP, induce increased neuronal firing (Nisenbaum et al, 1994) and are also potent convulsants (Gandolfo et al, 1989;Bagetta et al, 1992).…”

“…of neuronal firing (Bargas et al, 1989;Nisenbaum et al, 1994;Koyano et al, 1996). Thus, it can be concluded that the 4-AP-induced EEG discharges are the result of an increment in frequency firing, combined with an increased excitatory glutamate-and GABA-mediated synaptic transmission.…”

Developing a Neuronal Model for the Pathophysiology of Schizophrenia Based on the Nature of Electrophysiological Actions of Dopamine in the Prefrontal Cortex

“…As mentioned above, another major current that operates in the membrane voltage range just subthreshold to spike firing is a 4-aminopyridine-and dendrotoxin-sensitive slowly inactivating K ϩ conductance (Storm 1988;Hammond and Crépel 1992;Nisenbaum et al 1994Nisenbaum et al , 1996. This slow outward K ϩ current is responsible for membrane outward rectification in the depolarized voltage range and functionally opposes the sustained membrane depolarization mediated by the I NaP current to prevent PFC neurons from reaching firing threshold (Yang et al 1996a).…”

Modeling functions of striatal dopamine modulation in learning and planning

“…Medium spiny neurons fire with a maximal firing rate y max of about 6 Spikes per 100 msec (Apicella et al, 1992;Pineda et al, 1992;Nisenbaum et al 1994). A factor a = 0.3 Spikes/(100 msec * mV) is used to scale the firing rate to experimental data and is estimated from firing rates for constant current injections in the absence of dopamine agonists (estimated from figure 1 in Nisenbaum et al 1994; similar in figure 3 in Pineda et al, 1992). Eq.…”