The Cell PDF

The Cell ● Cytoskeleton: railroad tracks to maintain and support cells structure and function ○ ○ ○ ● Microfilaments made of ACTIN are smallest Intermediate filaments vary from cell to cell ■ Keratin ---> think skin -----> epithelium ■ Desmin ----> “you’d be a dead man without muscle” ---> muscle...

The Cell ● Cytoskeleton: railroad tracks to maintain and support cells structure and function ○ ○ ○ ● Microfilaments made of ACTIN are smallest Intermediate filaments vary from cell to cell ■ Keratin ---> think skin -----> epithelium ■ Desmin ----> “you’d be a dead man without muscle” ---> muscle ● ■ Vimentin -----> connective tissue (no memory tool just there kind of like CT itself) ■ GLIAL fibrillary acidic protein ---> NeuroGLIAL cells ■ NEUROfilaments ---> NEUROns ● Microtubules are the largest and made of TUBULIN Plasma Membrane is made of lipids ○ Cholesterol is responsible for membrane stiffening and rigidity ○ Phospholipids have a hydrophilic head and hydrophobic tail ■ Unsaturated means there's a kink and increases membrane fluidity G-protein coupled ○ ○ ○ Site of all things DNA and therefore gene regulation ● Has a double layered membrane Rough ER makes envelope that has nuclear pores for entering and exiting (only those with NLS can enter and those with NES can exit) NUCLEOLUS MAKES rRNA ER and Golgi ○ ○ ○ RER ----> all things proteins SER ---> all things steroids, fats and phospholipids Golgi ----> receives proteins on CIS side ----> modifies them -----> proteins exit on TRANS side Lead to a signaling cascade on activation of the G-protein Adrenergic and muscarinic receptors Ligand binding receptors (Ex: Insulin) ○ Nucleus ○ ○ ○ ● ● Requires something to bind to open the channel Gating ○ ○ ○ Voltage gated: CHARGE opens the gate (ex: sodium is positively charged molecule and can open some voltage gated channels) Ligand gated: extra or intracellular ligand binds to open gate Mechanically gated: stretch or pressure opens the gate Cell Excitation ● Electrochemical Gradient ○ Membrane potential = E net = E in - E out ● Driving Force ○ Driving force is the force(s) that cause ions to move into or out of the cell ○ Determined by the electrical gradient and the concentration gradient ○ If the electrical gradient and concentration gradients are in the SAME direction, there is a LARGE driving force ■ Na+ is mostly outside the cell so the concentration gradient pulls Na+ in the cell. Na+ is positively charged and the inside of the cell is negative so the electrical gradient pulls Na+ in the cell as well. Since both are pull Na+ into the cell it is said that Na+ has a LARGE driving force into the cell. (Na+ is the ion involved in depolarization of the cell so it makes sense that it’s driving force would be large. Hold this thought for later) ■ K+ is mostly inside the cell so the concentration gradient pulls K+ out of the cell but K+ is positively charged and the inside of the cell is negatively charged so the electrical gradient pulls K+ in the cell. The gradients are in opposite directions and therefore K+ has a SMALL driving force ● Depolarization ○ ○ ● Repolarization ○ ○ ● Cell becomes more POSITIVE (ie: the potential difference between the inside and outside DECREASES) This usually happens due to Na+ INFLUX Cell becomes NEGATIVE again --> returning to its polarized state This is usually caused by K+ EFFLUX Hyperpolarization ○ ○ ○ Cell becomes more NEGATIVE (past resting potential) This happens due to K+ EFFLUX Allows ion channels to recover before being re-excited Nerves and Neurons ● ● ○ ● Summation of EPSP (EPSP on their own don’t usually reach threshold for an AP) large and heavily myelinated Can be compressed --> loss of stimuli Touch, proprioception, motor function and some pain Include alpha, beta, gamma, and delta B fibers: ○ ○ ● Conduction Velocity ○ Velocity increases as diameter increases ○ Myelin increases velocity ■ Increases membrane resistance (keeps channels open) ■ Decreases capacitance ○ Length constant is inversely related to resistance of the axon ■ Increased diameter = increased length ○ (NOTE: axon resistance and membrane resistance are different!) Nerve Fibers A fibers: ○ ○ ○ ● ● Preganglionic of ANS Small and lightly myelinated C fibers: ○ ○ ○ Sympathetic from soma to periphery Small and unmyelinated ■ Local anesthetics work here Pain and temperature ■ Can still produce APs despite temperature decreases ○ ○ Temporal = two EPSP that happen close in time sum together to create an AP ■ Usually the second EPSP is happening before the end of the first Spatial = EPSP generated in synapses near each other can sum together to create an AP Neurotransmission Neurotransmitters Dopamine neurons in substantia nigra and ventral tegmental area ● ● Parkinsons ○ ● Steps in Neurotransmission (Chemical Synapse) ○ ○ ○ ○ ○ ○ NT is made in neuron and stored in vesicles AP causes depolarization down the neuron to the presynaptic nerve terminal Voltage gated Ca channels are activated and open allowing Ca to enter the presynaptic terminal Ca influx leads to vesicle fusion with plasma membrane and NT is released into synaptic cleft NT binds ionotropic or metabotropic receptor Signal is terminated by removal of NT from synaptic cleft ■ Enzymes can degrade NT in cleft ■ NT can be recycled into presynaptic terminal by reuptake Acetylcholine (ACh) ● Neuromuscular Junction (NMJ), presynaptic PNS and SNS and postsynaptic PNS ALZHEIMER’S DISEASE ○ ○ Amino Acid NT (Don’t get these confused, they all start with G) ● Glutamate: excitatory ---> prevents cell death (GlutaMATE is excited to be your mate :)) GABA: Inhibitory Glycine: Inhibitory ○ ○ ○ ● Receptor Types ○ ○ Ionotropic = Fast ■ ligand gated channels that respond to NT in milliseconds Metabotropic = slow ■ G-protein coupled channels that respond slow b/c they require a cased of signaling (cascades take time) Somatosensory System ● ● Dorsal Column: touch, vibration Somatosensory System ○ Body’s state and interaction with the world connection with CNS ○ Sensory receptors transduce information about pressure, stretch, etc. that are processed into electrical signals called receptor potentials ○ Receptor potentials = is “graded” which means it may or may not be strong enough to generate an action potential Receptors ○ ○ ○ ○ ○ Mechanoreceptors = equilibrium, pressure, movement, vibrations ■ Ex: touch receptor = pacinian corpuscle on skin Thermoreceptors = cold and warm ■ Ex: cold and warm receptors on the skin Nociceptors = pain ■ Ex: Polymodal or thermal nociceptors on the skin Electromagnetic receptors = vision ■ Ex: Photoreceptors are rods and cones in the retina Chemoreceptors = taste, smell, O2, CO2, osmolarity ■ Ex: pH of CSF in ventrolateral medulla Ascends ipsilaterally in dorsal column crosses midline in medulla and then ascends contralaterally in medial lemniscus. Spinothalamic Tract: pain and temp Crosses midline in spinal cord and ascends contralaterally in the ventrolateral quadrant Pain ● ● ● ● ● ● ● ● ● ● ● Allodynia = Pain from a stimulus that is not normally painful Dysesthesia = Unpleasant sensation Hyperalgesia = increased pain from a stimulus that normally causes a lower level of pain Hyperesthesia = increased sensitivity to a mild stimulus (no special senses) Hypoesthesia = decreased sensitivity to stimulation (no special senses) Hyperpathia = abnormally painful reaction to stimulus, especially a repetitive stimulus Hypoalgesia = diminished response to a normally painful stimulus Paresthesia = abnormal sensation (numbness/tingling) Neuropathy = disturbance of function of a nerve Neuralgia = pain in the distribution of a nerve Analgesia = absence of pain to a normally painful stimuli ● Pain Fibers ○ ○ ○ A beta: LARGE, proprioceptive fibers A delta: small myelinated skin fibers that respond to mechanoreceptive pain ■ Quick, intense, acute pain ■ Respond to mechanical and mechanothermal stimuli ■ Transmit APs 10 times faster than C fibers ---> first pain C: small unmyelinated fibers that respond to nociceptive pain ■ Throbbing, burning pain ---> second, longer lasting pain ■ Respond to thermal, mechanical and chemical stimuli ● Neuropathic Pain ○ Shooting, electric shock like aching or burning ○ Ex: referred pain --> pain (usually from an organ) is felt at a distant site. ● Tolerance ○ Drug tolerance: less efficacy in pain reduction from the same dose over time. ■ Require larger doses for the same effect---> increasing tolerance Autonomics ● Parasympathetic ○ Long preganglionic fibers that release ACH onto a nicotinic receptor on a short postganglionic fibers that release ACh onto a muscarinic receptor on the target organ ● Sympathetic ○ short preganglionic fibers that release ACh onto nicotinic receptors on long postganglionic fibers that release NE onto an alpha or beta adrenergic receptors on the target organ ● Fibers releasing ACh are cholinergic and fibers releasing NE (or Epi) are Adrenergic ACh ○ Receptors are muscarinic or nicotinic ○ Constricts pupils, constricts bronchioles, contracts detrusor muscle, erection, tears, decreased heart rate NE ○ Adrenergic receptors are alpha or beta and those are further divided into alpha 1 and 2 and beta 1 and 2 (so much more on this to come) ■ Alpha 2 are inhibitory and beta 2 are excitatory ■ Autoreceptor: respond to NT released by cell ■ Heteroreceptor: respond to NT released from surrounding ○ Dilates pupils, dilates bronchioles, relaxes detrusor muscle, constricts blood vessels, increases heart rate ● ● Smooth Muscle ● ○ ○ ○ ○ ○ ○ ○ Calcium from the ECF opens Ca channels on the sarcoplasmic reticulum (ICF) ---> “Ca induced Ca ● release” ■ Voltage -gated ■ Ligand gated ■ IP3 gated Ca binds calmodulin (Ca-CaM) MLCK is activated and binds Ca-CaM This starts the cross-bridge cycle Steps in Relaxation NE and Epi ○ Steps in contraction ○ ● ● ● Ca is removed from the ICF ■ SERCA pump ■ Ca-ATPase pump ■ Ca/Na exchanger Myosin phosphatase is activated by Ca decrease ■ Controlled by Rho Kinase ● MLCK is turned off and Contraction stops Contraction via alpha 1 receptor ----> Gq pathway (IP3) Relaxation via beta 2 receptor -----> Gs pathway (cAMP) ACh ○ ○ Contraction via M receptor on Smooth muscle cell ---> Gq pathway Relaxation via M receptor on endothelial cell ---> Gq pathway Calcium sensitization ○ ○ ○ Agonists increase force of contraction Due to decreased myosin phosphatase activity ■ Regulated by Ca levels and controlled by Rho kinase LEFTWARD shift Desensitization ○ ○ RIGHTWARD shift High myosin phosphatase activity