Nerve Impulses, Synapses, Reflexes and Muscle Contraction

Resting potential (about $-70\ \text{mV}$, inside negative) is set up by three processes together: the $\mathrm{Na^+}$/$\mathrm{K^+}$ pump (active transport, using ATP from respiration) moves 3 $\mathrm{Na^+}$ out for every 2 $\mathrm{K^+}$ in; $\mathrm{K^+}$ then leaks out through open channels by facilitated diffusion; and the membrane is much less permeable to $\mathrm{Na^+}$.

• An action potential is all-or-nothing: below threshold nothing happens, above it the size is always the same. A stronger stimulus gives more impulses per second, not bigger ones.
• The refractory period (sodium channels cannot reopen at once) keeps impulses separate and makes them travel one way along the axon.
• Speed: faster in myelinated axons, where the impulse jumps between the nodes of Ranvier (saltatory conduction); faster in wider axons; faster at higher temperature. The length of the axon does not change the speed, and synapses slow transmission down.
• Local anaesthetics block voltage-gated $\mathrm{Na^+}$ channels, so the membrane is harder to depolarise and no impulse reaches the brain.

A cholinergic synapse uses acetylcholine (ACh) as its neurotransmitter.

• Transmission is one way because vesicles of ACh are only in the presynaptic knob (released by exocytosis) and the ACh receptors and their linked ion channels are only on the postsynaptic membrane. The enzyme that breaks ACh down only stops the signal; it is not what makes it one way.
• Summation: several small inputs, from different neurones at once (spatial) or one neurone firing quickly (temporal), may add up to reach threshold. Inhibitory synapses make the postsynaptic cell harder to excite.
• The neuromuscular junction is a synapse between a motor neurone and a muscle fibre. It uses ACh and is always excitatory.
• Drugs act here: curare blocks ACh receptors (paralysis); nerve gases and some insecticides block acetylcholinesterase, so ACh stays and muscles go into spasm.

• Central nervous system (CNS): brain and spinal cord. Peripheral nervous system: all the nerves outside them.
• The somatic system controls skeletal muscle (voluntary); the autonomic system controls glands, cardiac muscle and smooth muscle (involuntary).
• Reflex arc: receptor, sensory neurone (enters the spinal cord at the back), relay neurone in the CNS, motor neurone (leaves at the front), effector. With these three neurones there are two synapses, both inside the CNS.
• The sympathetic (fight or flight) and parasympathetic (rest and digest) systems work in opposition on the same organs.
• Sympathetic ganglia lie close to the spinal cord (short first neurone, long second neurone); parasympathetic ganglia lie in or near the target organ (long first neurone, short second neurone).
• Both systems release ACh at their ganglia. At the target organ, sympathetic neurones mostly release noradrenaline and parasympathetic neurones release ACh.

A skeletal muscle is made of muscle fibres (long cells with many nuclei). Each fibre is packed with myofibrils, which are chains of sarcomeres. The fibre has many mitochondria and a sarcoplasmic reticulum that stores $\mathrm{Ca^{2+}}$; T-tubules carry the impulse into the fibre.

• Thick filaments: myosin. Thin filaments: actin, with the regulating proteins tropomyosin and troponin.
• Sliding filament model: in contraction the thin filaments slide between the thick ones towards the centre. The Z lines move closer and the sarcomere shortens; the filaments keep their length.
• Three muscle types: skeletal (striped, voluntary, many nuclei per cell); cardiac (striped, branched cells joined by intercalated discs, myogenic, involuntary); smooth (no stripes, spindle-shaped cells, involuntary, in the gut, airways and vessel walls).

• The myosin head is the ATPase: it hydrolyses ATP to re-cock itself. Actin and tropomyosin have no ATPase activity.
• $\mathrm{Ca^{2+}}$ binds troponin, not tropomyosin, myosin or actin.
• ATP binding to the myosin head makes it detach from actin. Without ATP the heads stay locked on, which is why muscles stiffen after death (rigor mortis).
• ATP is also needed to pump $\mathrm{Ca^{2+}}$ back into the sarcoplasmic reticulum, which lets the muscle relax.
• In hard exercise muscles also respire anaerobically; lactate builds up and muscle pH falls, while more blood is sent to the working muscles.