Cell 201: Signal transduction

What creates the resting membrane potential in neurons?

The separation of charge across the membrane due to uneven distribution of ions (K⁺ inside, Na⁺/Cl⁻ outside) and impermeable negatively charged proteins inside the cell.

What is the approximate value of the resting membrane potential in neurons?

–70 mV (inside of the neuron is 70 mV more negative than the outside).

What does the Na⁺/K⁺ pump do?

Actively transports 3 Na⁺ out and 2 K⁺ in to maintain the resting membrane potential.

What is the purpose of the absolute refractory period?

To prevent a second action potential from firing, ensuring unidirectional signal transmission.

When can a second AP occur during the relative refractory period?

Only if a stronger-than-normal stimulus is applied (neuron is hyperpolarized).

What glial cells form myelin in the CNS and PNS?

Oligodendrocytes in the CNS, Schwann cells in the PNS.

What is the "kiss and run" exocytosis mechanism?

A rapid NT release method where vesicles briefly fuse with the membrane, then detach to be reused.

How are chemical and electrical synapses different?

Electrical = fast, gap junctions, rare; Chemical = slower, NTs, more common and modifiable.

What does nAChR do?

It’s an excitatory ligand-gated receptor at the NMJ activated by ACh/nicotine → allows Na⁺ influx → triggers AP.

What blocks nAChRs?

Curare (causes muscle paralysis).

How does GABAa receptor activation inhibit firing?

It causes Cl⁻ influx → hyperpolarization → harder to fire an AP.

What enhances GABAa activity?

Benzodiazepines (e.g. Valium), Alcohol.

What blocks GABAa receptors and can cause seizures?

Bicuculline.

What are two main methods of neurotransmitter inactivation?

Reuptake (e.g., dopamine, serotonin) and enzymatic degradation (e.g., ACh via AChE).

What drugs block neurotransmitter reuptake?

SSRIs (serotonin), cocaine (dopamine).

What does botulinum toxin do?

Blocks presynaptic release of ACh → prevents muscle contraction.

How does endocrine signaling work?

Ligands (hormones) are secreted into the bloodstream and act on distant target cells.

What is paracrine signaling?

Local signaling; ligand diffuses through extracellular space to nearby cells.

What is juxtacrine signaling?

Direct cell-to-cell contact via membrane-bound ligands and receptors.

What is autocrine signaling?

A cell targets itself by binding its own released signal.

What are three key properties of ligand-receptor interactions?

Saturability (limited receptors), specificity (selective binding), and reversibility (ligand can detach).

What is the function of a signal transduction cascade?

Amplifies cellular responses using second messengers; allows for regulation and integration.

Where is Ca²⁺ stored in cells?

Endoplasmic reticulum, sarcoplasmic reticulum, and mitochondria.

How is Ca²⁺ removed from the cytosol?

Ca²⁺-ATPase pumps and Na⁺/Ca²⁺ exchangers.

What is calmodulin?

A calcium-binding protein that changes shape when bound to Ca²⁺ and activates target proteins.

2 Ca2+ bind at each “hand” of CaM → conformational change → Calcium-calmodulin complex

What are GPCRs?

7-transmembrane domain receptors that activate G-proteins upon ligand binding.

What are Ca2+ indicators?

Molecules that only fluoresce (green fluorescent protein; GFP) when bound to Ca2+

How ca you modify Ca2+ levels?

via Ca2+ ionophores; channels you can add into a cell to induce an increase in Ca2+ release

What do receptor kinases do?

Phosphorylate proteins to trigger downstream signaling.

What is SDS-PAGE used for?

Protein separation by size using polyacrylamide gel and SDS (denatures + adds uniform negative charge).

What is a Western blot?

Detects specific proteins using antibodies after SDS-PAGE separation and membrane transfer.

How do water-soluble hormones act?

Bind to surface receptors (e.g., GPCRs, RTKs); cannot cross membranes.

How do lipid-soluble hormones act?

Cross membrane and bind to nuclear/cytosolic receptors → act as transcription factors.

What do adrenergic hormones do?

Activate the sympathetic NS and promote glycogen breakdown for energy.

What is signal integration?

Multiple signaling pathways converging on shared targets inside a cell.

What is scaffolding in signaling?

Use of anchor proteins to organize and speed up signaling cascades.

What are lipid rafts?

Membrane domains rich in signaling proteins to facilitate efficient signal transduction.