Human Physiology Exam 1 (L1-L6)

Two components of extracellular fluid

Plasma, interstitial fluid

Intracellular fluid

Cytoplasm, fluid contained within plasma membrane of all body cells

There is direct contact between cells and blood

FALSE. Oxygen and nutrients are dissolved in plasma, not blood.

There are X types of cells. The typical human cell is Y microns in size.

~200, 10-20

Cells are held together by three different means.

1) The extracellular matrix

2) Cell adhesion molecules in the plasma membrane

3) Specialized cell junctions

Extracellular matrix (ECM)

A meshwork of proteins in a watery like substance that serves as a biological “glue”. Secreted locally by cells. Most abundant in connective tissue.

Basal lamina (basal membrane, basement membrane)

Thin mat of extracellular matrix that separates epithelial sheets (or other varieties of cells) from connective tissue

The four main functions of the basal membrane

BArry MEets FIona IN the basal membrane.

1) barrier

2) mechanical support for epithelia

3) filtering in kidney cells

4) influence cell polarity

Cadherins are cell adhesion molecules

N-terminal (side-to-side) cadherin repeats of adhered cells associate with each other with relatively low affinity. However, large numbers of interactions —> strong, stable adhesion (VELCRO PRINCIPLE)

Three types of specialized cell junctions

A) Desmosomes

B) Tight junctions

C) Gap junctions

Desmosomes

Cell junction in tissues that stretch (skin, heart, uterus); spot rivets, connect cells w/out direct contact

Tight junctions

Cell junction to form distinct, leak-proof regions, found primarily in epithelial tissue

Apical plasma membrane v.s. lateral plasma membrane v.s. basal plasma membrane

Tight junctions serve to separate different regions of the membrane. Prevent transmembrane proteins from moving outside designated region.

Apical - free surface, external

Lateral - sides, neighboring cells

Basal - bottom, basal lamina

Gap junctions (communicating junctions)

Cell junctions formed by connexons found most often in cardiac and smooth muscle (can be found in nonmuscle cells); make channels that allow for direct cell communication/exchange of nutrient molecules

Three types of carrier-mediated active transport

1) uniport

Coupled transport:

2) symport

3) antiport

Three major types of protein filaments in cytoskeleton:

1) actin filaments

2) microtubules

3) intermediate filaments

Cristae (mitochondria)

Folds of the inner membrane, containes proteins used in cellular respiration

Matrix (mitochondria)

Region enclosed by the inner membrane

Why do mitochondria need O2?

Final e- acceptor

Three cellular activities that require ATP

1) Synthesis of new chemical compounds

2) Membrane transport

3) Mechanical work

ATP Production

Glycolysis, CAC, ETC

Glycolysis

Glucose —> pyruvate, 2 NADH and 2 ATP

Citric acid cycle

Pyruvate is modified into acetyl-CoA, which enters cycle in mitochondrial matrix. Source of NADH and FADH2 for ETC. CO2 produced. ATP produced.

Electron transport chain

E- carriers in inner membrane (cristae). ATP is synthesized using E released by e- as they transfer to O2. (generate proton gradient, ATP synthase phosphorlates ADP)

Three types of intracellular communication

1) gap junctions

2) cell-to-cell binding

3) extracellular chemical messengers

Cell-to-cell binding

Surface molecules on two different cells bind to one another

Extracellular messengers: General flow of information

Receptor binding —> signal transduction —> cellular response

Chemical extracellular messengers can be water or lipid soluble

Water soluble: peptide/protein hormones, neurotransmitters, local mediators

Lipid soluble: steroids, thyroid hormones, NO2

Hormones

Extracellular chemical messengers that are carried by the blood to DISTANT target cells

Neurotransmitters

Extracellular chemical messengers released from neuron into synapse to reach NEARBY target cell

Local mediators

Autocrine and paracrine, self/local. Cytokines, nitric oxide, growth factors

Down-regulation of receptors

Excess of extracellular messengers can result in decrease number of target cell receptors

Up-regulation of receptors

Deficient messengers can result in increase of number of target cell receptors

Relay proteins

Secondary, intracellular messengers

Four conserved components of intracellular signal transduction pathways

1) second messengers

2) protein kinases and phosphatase

3) GTP binding proteins

4) protein ubiquitylation and degradation

Second messengers

Small, intracellular molecule lvls inc/dec upon binding of ligand. Short-lived. Activates downstream proteins.

Second messengers: cAMP

Activates PKA

Second messengers: cGMP

Activates PKG, open cation channels in rod cells

Second messengers: diacylglycerol (DAG)

Activates PKC

Second messengers: IP3

Opens Ca2+ channels in the ER

Second messengers: Ca2+

Produce/increase cell damage

Protein kinase

Activates target protein via transfer of phosphate to substrate

Reversible, so that future signals can be received

Protein phosphatases

Mediate removal (inactivation) of protein via removal of phosphate from substrate

Undoes what a kinase does

Phosphorylation is the most important post-translational modification of proteins. The two major types of kinases = two major types of phosphatases

STY

1) Serine/threonine

2) Tyrosine

GTPase superfamily of signal transduction proteins

Guanine nucleotide binding proteins. Two classes:

1) Trimeric (G-α proteins are associated with G protein-coupled receptors)

2) Monomeric (small, Ras superfamily)

GTPase switch proteins (G-proteins)

switch between active (phosphorylated, GTP) and inactive (bound by GDP) states

G-proteins are regulated by guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP)

GEF —> activator (think: excite)

GAP —> inactivator (think: active to inactive)

Three main classes of cell surface receptors

1) GPCRs

2) Enzyme-coupled

3) Ion-channel-coupled

GPCRs flow

1. The inactive form of GPCR:

2. G-protein is bound by ? and ? is phosphorylated.

3. The ? subunit, dissociates and binds the target protein.

4. GTP is ?.

5. The complex reassociates with the G-protein, and it returns to its ? state.

1. The inactive form of GPCR: G-protein, α-GDP, γ subunit, β subunit

2. G-protein is bound by ligand and GDP is phosphorylated (activated).

3. The α-GTP subunit dissociates and binds the target protein.

4. GTP is dephosphorylated (GDP).

5. The complex reassociates with the G-protein, and it returns to its inactive state.

The GPCR that is coupled to ? activates the secondary messenger cAMP.

Reminder: cAMP activates…

adenylyl cyclase

protein kinase A

Enzyme-coupled receptor responses are typically ?, but highly ?.

Enzyme-coupled receptor responses are typically slow, but highly sensitive.

Main types of enzyme-coupled receptors

1) Kinase itself: receptor tyrosine kinase family

2) Associate and activate a kinase

3) Guanylyl cyclase receptors: cGMP activates protein kinase G

Ion-channel-coupled receptors are responsible for the rapid transmission of signals across

neuron synapses

(When ligand binds receptor, ion channel opens)

Signal termination

All pathways must eventually be terminated:

1) Dissociation of messenger from receptor

2) Inactivation of signal transduction pathway components

Nervous v.s. endocrine system

1) Messenger molecules

2) Site of mediator action

3) Target cells

4) Onset time

5) Duration

1) neurotransmitter, local; hormone, far

2) Close; far

3) muscle, gland, neuron; cells throughout

4) FAST ms; varies

5) generally briefer, ms; generally longer s to d

All cells establish a membrane potential.

TRUE. Uneven distribution of ions —> polarized separation of charges across membrane.

Key ions involved in membrane potentials

Na+ is predominantly OUTSIDE

K+ predominantly INSIDE

Cl-

Generating a membrane potential

1) Membrane has no potential.

2) Pump artificially generates potential.

3) Charges align along membrane.

Rank the membrane permeability (hi to lo) of the folllowing ions

Na+, K+, A-

K+, Na+, A-

Slightly permeable, almost impermeable, not permeable

Rank the extracellular membrane concentration (hi to lo) of the folllowing ions

Na+, K+, A-

Na+, K+, A-

Resting membrane potential

-70 mV

Membrane electrical states: polarization

Membrane potential ≠ 0 mv

Membrane electrical states: depolarization

Membrane potential becomes less negative (polarized)

Membrane electrical states: repolarization

Membrane potential returns to resting potential after having been depolarization

Membrane electrical states: hyperpolarization

Membrane becomes more negative (polarized) than at resting potential

Graph the types of changes in membrane potential

Because the ions regulating potential cannot permeate the plasma membrane, they must cross via channels or carrier-mediated support. List the two types of membrane channels and their subtypes.

1. Leak channels

2. Gated channels

   1. voltage-gated

   2. Chemically-gated

   3. Mechanically-gated

   4. Thermally-gated

The two basic forms of electrical signals in neural communication

Graded potentials: short distance

Action potentials: long distance

What makes a potential “graded”?

Duration of signal is directly proportional to the strength and duration of the triggering event. Dies out over short distances. No refractory period.

Current flow during a graded potential

Triggering event opens Na+ channels, Na+ flows intracellularly and partially neutralizes negative charge. Depolarization spreads across membrane, resulting in movement of the current.

5 examples of graded potentials

PREPS

Postsynaptic

Receptor

End-plate

Pacemaker

Slow-wave

When a graded potential reaches a certain threshold, it can initiate an Action Potential

Brief, rapid, large (100 mv) changes in membrane potential during which potential actually reverses. Trigger involves a small portion of excitable membrane. Do not decrease in strength as current travels.

Once initiated, action potentials are conducted throughout a nerve fiber. Action potentials are propagated from

The axon hillock to the axon terminals

Draw the signal traveling through the neuron.

Dendrites —> cell body —> axon hillock —> axon + myelin sheath —> axon terminals

List the input zone, trigger zone, and output zone of the neuron

Dendrites, axon hillock, axon terminals

Voltage-gated sodium channel

Resting potential: all channels are closed

Reach threshold: channel opens

Action Potential: Influx of Na+ begins to neutralize negative charge —> depolarization

Peak: Na+ inactivaion gate begins to close, K+ gate opens

Repolarization: Efflux of K+

Hyperpolarization: Na+ inactivation gate begins opens, Na+ activation gate closes, K+ gate closes (gates are capable of reopening) —> restoration of resting potential

Propagation of action potentials: contiguous conductino

Local current flow that depolarizes adjacent inactive area from resting to threshold

Propagation of action potentials: contiguous conductino

Local current flow that depolarizes adjacent inactive area from resting to threshold

Refractory period

Ensures that the action potential is unidirectional. “Backward” current flow does not re-excite previously active area. (Recall voltage-gated channels. Gates are closed, and it takes time for them to reopen.)

All of None Law of action potentials

Stimulus must depolarize to threshold (-55/-50 mV) to induce action potential. Unlike graded potentials, the amplitude does not vary in response to signal strength.

How does stimulus strength relate to action potential?

Increase in stimulus strength —> more frequent action potentials

Myellin

Composed of lipid, insulates axon. Formed by oligodendrocytes of CNS or Schwann cells of PNS.

Nodes of Ranver

non-myelinated areas of the axon, exposed to the extracellular fluid

Propagation of action potentials: Saltatory Conduction

Action potential impulses jump from node to node, drastically increasing the speed of conduction (50X). Bypasses need to regenerate action potential.

The three termination sites of neurons

1) Muscle-cell contraction

2) Gland-cell secretion

3) another neuron-synapse

Synapses and chemically-gated ion channels

1. Action potentials reach axon terminals.

2. Voltage-gated Ca2+ channels open.

3. Ca2+ binds to sensor protein n cytoplasm.

4. Ca2+-protein complex stimulates fusion and exocytosis of neurotransmitter (to post synaptic cell).

Two types of synapses

Excitatory and inhibitory

Central nervous system (CNS) consists of

Brain and spinal cord

The peripheral system consists of the

Afferent division and efferent division

Afferent division (PNS)

Carries sensory and visceral stimuli to the CNS

Efferent division (PNS) and its two divisions

Carries information away from CNS to effector organs, consists of somatic nervous system and autonomic nervous system

Autonomic nervous system consists of two further subdivisions

Sympathetic and parasympathetic nervous systems

Interneuron (association neurons)

Found in the CNS, lies between afferent and efferent neurons (peripheral responses to peripheral information). Associated with abstract phenomena (mind, emotion). 99% of all neurons are interneurons.

Describe the connection of sensory, somatic motor, and autonomic motor neurons to the spinal cord.

Sensory neurons are directly connected to the spinal cord. Termini are closely associated with the dendrites of interneurons.

Somatic motor neurons are directly connected to the spinal cord via their cell bodies.

Autonomic motor neurons are associated with efferent neurons whose cell bodies are embedded in the spinal cord.

The CNS is mostly (90%) composed of glial or neuroglial cells. Definition and four types?

Connective tissue of the CNS, do not initiate or conduct nerve impulses.

1) astrocytes

2) oligodendrocytes

3) microglial cells

4) ependymal cells

Astrocytes

4 main functions?

Neurotransmitter?

Other roles?

Main “glue” of CNS. Direct neural fetal development, establishment of blood brain barrier, brain injuries and neural scar formation.

Glutamate receptors, communicate by gap junction.

Learning and memory, thrombospondin enhances synapse formation/transmission. Take up excess K+ from brain ECF.

Reminder: Oligodendrocytes form X around axons in CNS?

Myelin sheaths

Microglia

Immune defense cells of CNS (can relate to autoimmune/neurodegenerative disease). At rest, release growth factors.

Ependymal cells

NEURONAL STEM CELLS. Line internal, fluid-filled cavities of CNS. In ventricles of brain, help form and circulate cerebrospinal fluid.

Protection of CNS

Bony structures: cranium (skull) and vertebral column

Meninges (membranes): Dura, arachnoid, pia maters

Cushioned by cerebrospinal fluid

Blood-brain barrier