User:ThrowTheBar2/SK Channel Outline

SK Channel Outline

Small Conductance Calcium-activated Potassium (SK) Channel

Classification
a. Channel protein that is voltage independent b. Found in the CNS (microglial cells) and PNS

c. There are subtypes of SK channels;

i. KCa2 channels (KCa2.1, KCa2.2, and    KCa2.3)

ii. KCa3.1 intermediate conductance channel

Structure
a. Functional SK/KCa2 channels consist of four sub-units composed of six trans-membrane regions

b. In mice, and likely humans, SK channels are localized to dendritic spines

Function
a.SK/KCa2 and IK/KCa2 channels elucidate their multifaceted functions in cell motility, neuronal excitability, neuroprotection, and neuroinflammation i.Regulate the excitability of rat midbrain neurons b.Small molecules or toxins seem to reveal critical roles of  SK3/KCa2.3 channels in microglial activation i.These channels contribute to action potential frequencies

c. Modulation of channel revealed other possible functions i. synaptic plasticity

d.SK/KCa2 channels act as fine tuning regulators of action potential frequencies, neuronal excitability, and [Ca2+] i.SK/KCa2.2-containing channels are responsible for precision of action potential timing

e.SK/KCa2 channels are emerging candidates to control N-Methyl-D-aspartic acid receptors

Blockers
a. Apamin or tamapin can inhibit SK channel function in certain microglial cells i. Apamin's only mechanism of action is to block SK channels this mechanism does not work on all SK channels however

Modulators
a. Riluzole, a drug used in patients with amyotrophic lateral sclerosis (ALS) and hereditary cerebellar ataxia, is a potent activator of SK/KCa2

Role in Parkinson’s Disease
a. Neuroinflammation is a critical indicator for this disease and SK Channel degradation can increase levels of neuroinflammation i.SK/KCa2 channel activity elicits a dual mechanism of action with direct protective effects in neuronal cells and inhibition of inflammatory activities in    microglial cells

b.Modulation of SK/KCa2 channels in dopaminergic neurons regulates neuronal excitability, survival, and neurotransmitter release, making them suitable candidates for therapeutic intervention in pathological conditions related to dopaminergic dysfunction, such as Parkinson’s disease