HCN hyperpolarization-activated cation channels strengthen virtual nicotinic EPSPs and thereby elevate synaptic amplification in rat sympathetic neurons

The influence of hyperpolarization-activated cation current (h-current; I_h) upon synaptic integration in paravertebral sympathetic neurons was studied together with expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) subunit isoforms. All four HCN subunits were detected in homogenates of the rat superior cervical ganglion (SCG) using the PCR to amplify reverse-transcribed messenger RNAs (RT-PCR) and using quantitative PCR. Voltage clamp recordings from dissociated SCG neurons at 35°C detected I_h in all cells, with a maximum hyperpolarization-activated cation conductance of 1.2 ± 0.1 nS, half-maximal activation at –87.6 mV, and reversal potential of –31.6 mV. Interaction between I_h and synaptic potentials was tested with virtual fast nicotinic excitatory postsynaptic potentials (EPSPs) created with dynamic clamp. The blocking of I_h with 15 μM ZD7288 hyperpolarized cells by 4.7 mV and increased the virtual synaptic conductance required to stimulate an action potential from 7.0 ± 0.9 nS to 12.1 ± 0.9 nS. In response to stimulation with 40 s long trains of virtual EPSPs, ZD7288 reduced postsynaptic firing from 2.2 to 1.7 Hz and the associated synaptic amplification from 2.2 ± 0.1 to 1.7 ± 0.2. Cyclic nucleotide binding to HCN channels was simulated by blocking native I_h with ZD7288, followed by reconstitution with virtual I_h using a dynamic clamp model of the voltage clamp data. Over a 30-mV range, shifting the half-activation voltage for I_h in 10 mV depolarizing increments always increased synaptic gain. These results indicate that I_h, in sympathetic neurons, can strengthen nicotinic EPSPs and increase synaptic amplification, while also working as a substrate for cyclic nucleotide-dependent modulation.

from Physiology via xlomafota13 on Inoreader http://ift.tt/2ataWzO
via IFTTT