L13 Flashcards
Diff pathologies in excitable cells
Heart:
Sino-atrial node - pacemaker activity HCN
Cardiac myocyte - ventricular AP (hERG)
Pancreas:
insulin-secreting ß cells - sensing glucose (Kir6.2)
3 phase cycle
Electrical activity in the heart and the current/ion channels that contribute to pacemaker activity
0 - upstroke. Ca2+ current, slow depolarisation
3 - repolarisation. K+ current repolarisation
4 - pacemaker. If pacemaker current, It subthreshold Ca2+ current
If pacemaker current
supports AP
inward current, but activated by hyperpolarisation at -50 to -40. opposite to conventional voltage channels, hence FUNNY
HCN
Hyperpolarisation activated Cyclic Nucleotide-gated channels
CNBD
Cyclic Nucleotide (cGMP/cAMP) Binding Domain shifts voltage - dependence of activation to a more +ve level
Automatic modulation
Heart controlled by parasympathetic input (VAGUS), Ach release slows pacemaker firing
Spinal nerve increases HR through sympathetic input, noradrenaline speeds up pacemaker firing rate
HCN drugs
Ivabradine is a HCN blocker, slows HR
also for chronic stable angina
K+channels with unusual features
partial inactivation at >0mV
if QT isnt spot on, complications. Na+ doesn’t deactivate.
prolonged AP is bad
Long QTs –> arrhythmias, loss of consciousness, death
what are long QTs?
Abnormally long interval between onset of excitement and contraction of ventricles and their subsequent relaxation.
12+ LQT genes, hard to test drugs
islets of longerhans
dotted around the pancreas
ß cells stimulate glucose uptake, metabolism and storage following ingestion of carbs and reduces extracellular levels.
K.ir6.2
What are islets of lonerghans made up of
four inward rectifiers K.ir6.2 (closed), and four SUR1s (open)