Explain how calcium homeostasis is maintained, and outline the common disorders

of this
I.
General principles
a. Electrical gradients
i. The cell membrane is impermeable to small, highly charged ions.
ii. When large number of ions are congregated on one side of the membrane, a gradient
is formed.
iii. The gradient is based on a difference in electrical potential on either side (the
difference in positive/negative charges) and on the concentrations of the ions (the
chemical gradient)
iv. The electrical gradient is a high energy state and relieving the gradient creates a
force eg: This is the energy used to synthesize ATP in mitochondria
v. Gradients are measured relative to the two sides of the plasma membrane. This
means that the exterior of a cell is always arbitrarily designated as 0 mV, while the
interior is given a number either positive or negative (or 0 at equilibrium)
b. Ion movement
i. Since Ions cannot move across the membrane, protein transporters are required
ii. Transporters can be active or passive, and can be ligand gated (activated by a
ligand), voltage gated (activated by an electric potential), mechanical (activated by
pressure, sound ect)
iii. Rate of movement depends on the type of channel and the total number
c. Potential differences
i. Average potential difference for a resting neuron is -70mV
ii. Trapped ions (proteins and phosphate) and diffusible ions (Ca, K) contribute to the
potential difference
iii. K ions are more permeable than Na, which is why partly why the interior of the cell is
more negative
iv. The Na/K ATPase maintains resting equilibrium in most cells. 3x Na removed from the
cell for every 2x K entering
v. A theoretical concept Equilibrium potential- Is the electrical gradient required to
balance an Ion against its chemical gradient. At this electrical gradient the rate of
transfer of an ion in and out of a cell is equal and there is no potential energy to do
work.
vi. To calculate the equilibrium potential of a SINGLE ION a modified version of the
Nernst Equation is used.

E=

II.

[ inside cell ]
RT
ln (
)
nF
[ OutsideCell ]

1. For multiple ions the Goldman Equation is used

Generation of electrical signals in neurons
a. Action potentials are used to transmit signals across long distances, as opposed to
graded potentials which transmit over short-distance in dendrites and cell bodies
b. Graded potentials are small deviations from the resting potential
i. The deviations can cause slight hypo- or hyperpolarization depending on the stimulus
ii. GPs begin when mechanically- or ligand-gated ion channels are opened or closed
iii. Called graded because they vary in intensity dependant on the strength of stimulus
iv. GPs have no way of focussing the wave of depolarization, which is why they are only
useful for short-distance
c. Action potentials are a series of events resulting in depolarisation and repolarisation of
the neuron to allow signal transmission

d. Action potentials are all-or-nothing actions, either a stimulus is too weak for an AP to fire
(subthreshold), the stimulus is exactly correct (threshold) or it exceeds the stimulation
required, resulting in multiple APs of equal amplitude to the threshold stimulus
e. Neurons have an absolute refractory period where a new AP cannot occur, and a relative
refractory period when it is harder to fire a new AP than during rest
f. An action potential is not a single event, it occurs across the axon multiple times, this is
called propagation.
i. Depolarization of a section of the axon causes a depolarising effect on nearby
sections due to the diffusion of sodium across the cytosol.
ii. However, because the membrane section behind the current action potential is in the
refractory period the ion channels do not reopen, allowing unidirectional propagation
of a neural signal
g. Myelinated nerve fibres are able to conduct signals much faster than unmyelinated
neurons due to saltatory conduction
i. Voltage gated ion channels are concentrated at the nodes of Ranvier in myelinated
neurons.
ii. During depolarization at the nodes, the influx of sodium forces intracellular ions along
the axon to the next node. An electric current is also formed extracellularly, both of
which cause depolarization at the next node.
iii. This gives the appearance of the signal skipping along the nodes, but is really an
almost instantaneous signal transduction
iv. This method allows conserving of ATP, allowing more energy-efficient signalling
h. Nerve conduction speed is dependent on diameter, myelination, and temperature
III.
Transmission across synapses
a. Electrical Signalling
i. An electrical synapse is the propagation of an action potential across gap junctions
between cells
ii. Gap junctions are tubular connecting proteins that allow a direct connection between
the cytosol of two cells
iii. Common in Visceral smooth muscle, cardiac muscle, and the brain
iv. The major advantage is that communication is quicker and it allows synchronization
of multiple muscle fibres (heart beats)
b. Chemical synapses
i. Synaptic cells do not touch or have direct cytosolic connection
ii. The synaptic space is 20-50nm
iii. The action potential is transferred across the synapse by a mediating ligand
iv. Synaptic delay in signal transmission results in a delay of 0.5ms vs electrical
synapses
v. Synapses can be axodendritic (Axon to dendrite, most common), axoaxonic, or
axosomatic (to cell body)
c. Stages of neurotransmitter release
i. The action potential makes its way across the axon to the synaptic end bulb
ii. Depolarization activates voltage gated Calcium channels which increases intracellular
Ca
iii. Calcium binding to vesicular proteins initiates exocytosis of neurotransmittercontaining synaptic vesicles into the synaptic cleft
iv. Neurotransmitters bind to receptors on the postsynaptic nerve, initiating the
postsynaptic potential and propagating the nerve signal
1. Receptors are either ion channels or GPCRs,
d. Excitatory or inhibitory postsynaptic potentials
i. Neurons can cause both excitatory or inhibitory actions on the postsynaptic nerve
ii. Inhibitory signals result in cellular hyperpolarisation, making action potential
generation harder
1. Normally results in Cl or K channel activation
iii. Excitatory signals cause cellular depolarisation
1. Normally Ca or Na channel activation
iv. These signals are graded potentials, therefore the total sum of all signals affects the
activation of the neuron
e. Neurotransmitter recycling
i. Neurotransmitters are either broken down enzymatically (Acetylcholine) or are
uptaken by the presynaptic neuron (serotonin)

f.

ii. Acetylcholine is lysed into acetate and choline by the postsynaptic cell, and then
reabsorbed and reformed by the presynaptic cell
Drug targets and poisons
i. SSRIs block the action of the serotonin transporter, causing increased levels in the
synapse and increase stimulation
ii. Acetylcholine esterase inhibitors used to treat dementia
1. Organophosphates inhibit the same enzyme, found in pesticides
and chemical weapons