Cocaine induced hyperpolarization of dopamine neuron cell membrane unexpectedly increases firing rate in an extracellular single unit recording of rat brain slice.
Perhaps hyperpolarizing the membrane allows a larger proportion of the voltage gated sodium channels to recover from inactivation in the interspike interval.
Removal of inactivation of voltage gated sodium channels as Michael above mentioned, removal of inactivation of T-type Calcium channels that also may participate in the generation of spikes and bursts and, increase in the hyperpolarization-activated potassium current, to mention some.
Additionally, hyperpolarisation of neural membranes can open voltage-gated non-specific cation channels known as a HCN (hyperpolarization-activated cyclic nucleotide-gated) channels. This causes an influx of positive charge (most likely carried by Na+ and Ca2+) known as an 'Ih' current that effectively depolarises the membrane potential. If it is strong enough, it can lead to an increased firing rate over the short term.
You can pharmacologically block HCN channels with ZD7288. A cheaper (but dirtier) alternative is Cs+. You could run on your cocaine with and without one of these and see if the increased firing rate is caused by an Ih current.
Jamie, since these are non-specific cation channels, do they also allow K+ to leave the cell?
You're right, they are also permeable to K+. However, because HCN channels open at relatively hyperpolarised potentials, the electrochemical driving force for Na+ and Ca+ into the cell is much higher than the electrochemical driving force for K+ out of the cell. This leads to an overall inward current (ie. positive charge going into the cell). You could check your library for 'Ion Channels of Excitable Membranes' by Bertile Hille which has a nice section on Ih current.
Hi Boris, can you elaborate on your answer please? What do you mean by cell input resistance?
Hi Boris, thank you for your explanation. Can you recommend a paper that employs cell resistance monitoring to discriminate between K+ channels opening versus non-selective cation (Na+) closing? Additionally, are there other techniques can I use besides injecting current pulses? Thanks.
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