Lecture 15- Neuronal cells + Gated ion channels

What is membrane potential and how is it maintained across the plasma membrane

Na+ flows in and K+ flows out defined by passive diffusion this is balanced by active transport of the ions in opposite direction by NA/K-ATPase. The separation of charge across the cell membrane forms membrane potential. A more negative charge inside the membrane and a more positive charge outside makes a transmembrane potential difference maintained across an impermeable lipid bilayer. Membrane potential is primarily based on 4 ion species: K+, Na+, Cl-, and organic anions. Membrane potential is between -50 and -70mV and its maintained by Na/K ATPase 3Na out for every 2K in.

How do ions move across gated ion channels

DEpolarization occurs by activation of the voltage gated Na+ channel in response to a brief current pulse. Rapid influx of Na ions changes plasma membrane potential to 50mV and the open stateis rapidly inactivated by a separate gate-inactivating mechanism. The rapid change in membrane potential activates the voltage gated K channels and a rapid eflux of K ions hyperpolarizing the plasma membrane and resets the Na channel to a closed state.

what is the acetylcholine receptor and how does it allow transmission of APs at neuromuscular junctions?

The receptor is a made of 5 subunits surrounding a central pore. When closed the pore is too small for ion passage. When the Ach binds to the Leu side chain of M2 helices it causes Ach receptor channels to twist open. Resulting in an influx of Na+ and Ca++ depolarizing the post synaptic cell. This receptor allows AP transmission.

How do voltage-gated ion channels propagate a neuronal action potential?

They propagate neuronal action potentials along an axon by depolarization and repolarization till the pulse activates Ca++ which causes fusion of presynaptic membrane and neurotransmitter vesicle. the end of the axon releases Ach into the synapse. Ach binds the Ach receptor of the target neuron or muscle and causes rapid depolarization and propagation to the target cell.

Na+ channel

the channel is made of a single polypeptide organized in 4 domains. Each domain has 6 trans-membrane helices. The pore region creates a Na+ specific pore which is found between trans-membrane helices of each domain. Helix#4 contains many positive charged amino acids that move when the membrane potential changes triggering channel opening. The cytoplasmic portion of the Na+ channel acts with the inactivation gate, they are attached. When closed the gate is free to move, when open a site on the channel allows for binding of the gate blocking the channel and closing.

K+ channel

MAde of 4 identical subunits that are membrane-spanning. The basis of K specificity is the pore region. The pore entry is concentrated with negatively charged amino acids that lets the interact with cations. The remainder of the pore is water lined. Narrowing the channel further in the membrane forces a loss of the ion-hydration cage. oo

How do neuronal AP work?

Impulse arrives at dendrite of cell body +spreads to axon that contains voltage-gated channels. Transmission of signal occurs down the length of the axon(AP). It uses voltage gated Na channels, then K channels, than Ca2+ channels. It reaches the terminal branches of the axon and neurotransmitter is released. It depolarizes teh post synaptic causing muscle contraction.

Activation of post synaptic neuron

Excitatory neurotransmitters depolarize post synaptic- Acetylcholine

Curare blocks Ach receptors, used as anaesthetic

Antidepressant(prozac), inhibit seratonin uptake

Inhibitory neurotransmitters hyperpolarize post syn- GABA

Valium(tranquilizer) bind GABA lowering [GABA] needed to activate Cl channels

An ion channel defect

A defect in the Cl ion channel affecting the CFTR gene causes cystic fibrosis