The dysfunction of potassium channels, including SK channels, is thought to play a role in the pathogenesis of Parkinson's disease (PD), a progressive neurodegenerative disorder.
SK channel blockers control the firing rate (the number of action potentials produced by a neuron in a given time) and the firing pattern (the way action potentials are allocated throughout time) through their production of m-AHP. SK channel activators decrease the firing rate, neuron sensitivity to excitatory stimuli, mediating neuroprotection, whereas SK channel blockers increase the firing rate and sensitivity to excitatory stimuli. This has important implications as to the function of dopaminergic neurons.  For example, the amount of dopamine released by midbrain dopaminergic neurons is much higher when the frequency of firing increases than when they fire at a constant rate.
SK channels are widely expressed in midbrain dopaminergic neurons. Multiple pharmacological techniques have been used to adjust SK affinity for calcium ions, thereby modulating the excitability of substantia nigra dopaminergic neurons.  Blockage of SK channels in vivo increases the firing rate of substantia nigra cells, which increases the amount of dopamine released from the synaptic terminals. When a large amount of dopamine accumulates in the cytosol, cell damage is induced due to the build-up of free radicals and damage to mitochondria. 
In addition, techniques have been used to modulate SK channels in order to alter the dopamine phenotype of neurons.  After the loss of TH+ (tyrosine hydroxylase-positive) substantia nigra compacta (SNc) neurons due to Parkinson’s-induced neurodegeneration, the number of these neurons can partially recover via a cell phenotype "shift" from TH- (tyrosine hydroxylase-negative) to TH+. The number of TH+ neurons can be altered by SK channel modulation; to be specific, the infusion of SK agonists into substantia nigra increases the number of TH+ neurons, whereas the infusion of SK antagonist decreases the number of TH+ neurons.  The reason for this relationship between SK channels and TH expression may be due to neuroprotection against dopamine toxicity.
Two contradictory methods have been suggested as therapeutic options for the improvement of PD symptoms:
Inhibition of SK channels
*Inhibition of SK channels, to be specific the blockage of SK3 channels, increases the frequency of firing in dopaminergic neurons, thereby increasing the release of dopamine.  It is, therefore, thought that the application of SK3 channels blockers in PD patients may alleviate short-term motor symptoms. 
*However, inhibition also results in a decreased number of TH+ substantia nigra compacta (SNc) neurons in the cell, which results in a decrease in dopamine synthesis over the long term. 
Facilitation of SK channels
*Enhancing the function of SK channels increases the number of TH+ substantia nigra compacta (SNc) neurons in the cell, thereby maintaining dopamine synthesis over the long term.
*However, the facilitation of SK channels decreases the firing frequency in dopaminergic neurons over the short term.