--- module: 002-01 language: en chapter: 2 title: "Membranes, Signalling, and Excitable Cells" module_title: "Foundations" source_sha256: 1166bd3bfef580b29dfcfc623eb4031de6cb5ebeead3e1516d6a1bf3e2dab0a7 --- # Membranes, signalling, and excitable cells ## Resting potential and the action potential ### Potassium high inside, sodium high outside ### Selective permeability and the sodium-potassium pump #### Inside negative relative to outside ### Graded potential scales with stimulus strength ### Threshold at trigger zone opens sodium channels #### Sodium entry produces the rising phase ### Sodium inactivation and potassium efflux repolarise #### Continued potassium conductance: brief hyperpolarisation ### All or none: stronger input raises frequency, recruitment ## Refractoriness and propagation ### Absolute refractory: inactivated sodium channels #### Cannot reopen even with a strong stimulus ### Relative refractory: potassium conductance persists #### A stronger input may succeed ### A changing molecular state, not energy exhaustion ### Refractoriness limits rate, enforces one-way travel ### Local current depolarises adjacent membrane #### Signal regenerated, ions not carried as a packet ### Myelin: saltatory conduction, renewed at each node ## Synapses and autonomic control ### Presynaptic calcium entry triggers release ### Ionotropic receptors: direct channels, fast ### Metabotropic receptors: pathways, slower, longer ### Excitatory potential moves toward threshold ### Inhibitory potential moves away or stabilises ### Spatial and temporal summation integrate inputs ### Autonomic control of cardiac, smooth muscle, glands #### Sympathetic mobilises, parasympathetic conserves #### Coordinated tendencies, many organs dual input ## Hormone classes and feedback ### Act only on cells bearing receptors ### Peptides and catecholamines: water-soluble #### Membrane receptors and second messengers ### Steroid and thyroid hormones: lipid-soluble #### Intracellular receptors alter gene expression #### Slower onset, longer lasting ### Thyroid axis: releasing hormone, stimulating hormone #### Rising thyroid hormone inhibits both levels ### Insulin and glucagon act antagonistically #### Insulin: uptake and glycogen, fat, protein synthesis #### Glucagon: glycogen breakdown and gluconeogenesis ### Adrenal medulla fast, cortisol axis slower ## Neural and endocrine integration ### Neurons: targeted, milliseconds to seconds ### Hormones: broad, seconds to days ### Hypothalamus converts neural input to endocrine output ### Hormones alter brain function and behaviour ## Sensory coding ### Transduction of energy into electrical signals ### Receptors selective rather than perfectly specific ### Intensity: firing frequency and recruitment ### Location: receptive field and pathway ### Adaptation reduces response to constant stimuli #### Rapid adapters signal change and vibration #### Slow adapters report magnitude or position ### Pain sensitises after injury #### Mediators and central pathways lower thresholds ## Motor hierarchy and reflexes ### Spinal circuits: reflexes and patterned activity ### Brainstem: posture, balance, eyes, breathing ### Cortex plans, basal nuclei select and scale ### Cerebellum compares intended with actual movement ### Stretch reflex: spindle excites same-muscle neurons #### Reciprocal inhibition of the antagonist #### Descending pathways adjust reflex gain ## Endocrine axes in detail ### Concentration: secretion, binding, metabolism, excretion #### Bound fraction a reservoir, free fraction acts #### Pulsatile and circadian timing matter ### Cortisol axis: releasing hormone to cortisol #### Excess: muscle breakdown, hyperglycaemia, bone loss #### Deficiency: poor pressure support and stress tolerance ### Growth hormone pulses, drives insulin-like growth factor 1 ### Prolactin tonically inhibited by dopamine ### Low calcium stimulates parathyroid hormone #### Kidney keeps calcium, loses phosphate #### Active vitamin D raises gut absorption ## Receptors, interaction, and plasticity ### Response: concentration, receptors, affinity, machinery #### Saturation flattens the dose-response #### Spare receptors allow maximal response ### Permissive, synergistic, antagonistic interactions #### Thyroid hormone permits catecholamine response ### Disease: excess, deficiency, resistance, feedback loss #### Primary failure: low thyroid, high stimulating hormone #### Pituitary failure: both inappropriately low ### Plasticity: synapses strengthen or weaken #### Long-term memory needs gene expression #### Can sustain chronic pain, addiction, fear