lecture 5: Neurophysiology and Protein Transport

The Na+ channels have an automatic inactivation mechanism that causes them to reclose rapidly.
- Inactivated State: The Na+ channel remains inactivated until the membrane potential returns to its initial negative value.
- Inactivation Gate: A flexible loop connecting the third and fourth domains acts as a plug that obstructs the pore in the inactivated state.

Repolarization Requirement: Requires opening of delayed K+ channels.
- These channels also respond to membrane depolarization but open during the falling phase of the action potential when Na+ channels are inactive.
- K+ Outflow: When delayed K+ channels open, K+ rushes out of the cell until the resting potential is restored.

Action Potential Progression: Propagation occurs along the axon as voltage changes with Na+ channels and voltage-gated K+ channels.
- Once initiated, the action potential travels only away from the depolarization site due to Na+ channel inactivation.

Passive Spread: A neuron is stimulated when dendrites receive a depolarizing stimulus.
- The depolarization spreads passively from the dendrite through the cell body to the axon hillock, where an action potential forms and propagates along the axon.

Myelin Sheath: Insulates axons of many vertebrate neurons, significantly increasing action potential conduction speed.
- Formation: Myelin is formed by glial cells that wrap their plasma membranes tightly around the axon.
- Nodes of Ranvier: Interruptions in myelin where Na+ channels are concentrated, allowing action potentials to jump from node to node (saltatory conduction).

Increases the speed of action potentials and conserves metabolic energy due to limited active excitation at nodes.

Signal Transmission: Neuronal signals are transmitted across synapses where presynaptic and postsynaptic cells are separated by a synaptic cleft.
Voltage-Gated Ca2+ Channels: Action potentials cause these channels in the presynaptic membrane to open, leading to Ca2+ influx and neurotransmitter release via exocytosis.
Transmitter-Gated Ion Channels: Neurotransmitters bind to these channels to induce electrical changes in the postsynaptic cell.

After release, neurotransmitters are quickly removed from the synaptic cleft either by enzymatic destruction or reuptake by the presynaptic terminal or glial cells, ensuring signaling precision.

Excitatory Neurotransmitters: Generally open nonselective cation channels, allowing Na+ and Ca2+ influx, depolarizing the postsynaptic membrane.
- Examples include acetylcholine and glutamate.
Inhibitory Neurotransmitters: Open Cl- channels, making it harder for excitatory stimuli to depolarize the cell, thereby suppressing firing.
- Examples include GABA and glycine.

Structure: Composed of five transmembrane polypeptides forming a transmembrane pore.
Binding Mechanism: Binding of acetylcholine to the receptor induces conformational changes that open the channel, allowing cation influx.

Nerve Impulse Arrival: Depolarizes the nerve terminal, opening voltage-gated Ca2+ channels.
Acetylcholine Release: Triggers release of acetylcholine into the synaptic cleft.
Binding to Receptors: Acetylcholine binds to receptors in muscle-cell membrane, causing cation channel opening and local depolarization.
Further Depolarization: Local depolarization opens voltage-gated Na+ channels, reinforcing the action potential.
Calcium Release: Activates voltage-gated Ca2+ channels in transverse tubules, leading to Ca2+ release from the sarcoplasmic reticulum into the cytosol.

Sorting Signals: Proteins have specific sorting signals that direct them to different cellular compartments.
**Transport Methods:
1. Transmembrane Transport: Direct transport via translocators.
2. Gated Transport: Movement through nuclear pore complexes.
3. Vesicular Transport: Transport via membrane-enclosed intermediates.
4. Engulfment: Such as in autophagy, wrapping cellular components for transport.

Diversity: ER is structurally diverse and involved in lipid and protein biosynthesis; it stores intracellular Ca2+.
Rough vs. Smooth ER: Rough ER has ribosomes; smooth ER lacks ribosomes and is involved in lipid synthesis.
Contacts with Other Organelles: Smooth ER makes contacts with mitochondria and plasma membrane for intracellular signaling and transport.

Microsome Formation: During cell homogenization, the ER fragments into microsomes for study purposes; they retain protein translocation abilities.

Signal-Sequences and Translocation: Essential for directing ribosome to the ER for protein synthesis, with a signal peptidase trimming the sequence during translocation.

Composition: Comprised of multiple polypeptides bound to RNA, guiding the ER signal sequence to its receptor at the ER membrane.
Signal Sequence Binding: Holds the signal as it emerges from the ribosome, pausing translation temporarily until proper positioning is achieved.

The Sec61 complex forms a water-filled channel for polypeptide translocation across the ER membrane. It remains closed when idle, preventing leakage of ions until the signal sequence activates it for transport.