Interstitial cells of Cajal (ICC) in the GIT serve as pacemaker cells generating the basic electrical rhythm (slow waves). The ionic mechanism responsible for pacemaker depolarization in ICC is primarily based on:
- A Hyperpolarization-activated funny current (If) through HCN channels similar to cardiac pacemaker cells
- B Spontaneous release of Ca²⁺ from IP3-receptor channels on the endoplasmic reticulum activating Ca²⁺-activated Cl⁻ channels (ANO1/TMEM16A) on the plasma membrane ✓
- C Periodic closure of K⁺ channels causing depolarization to threshold followed by L-type Ca²⁺ channel activation
- D Oscillatory Na⁺ leak currents through voltage-independent channels generating regular depolarizations
Correct answer: B. Spontaneous release of Ca²⁺ from IP3-receptor channels on the endoplasmic reticulum activating Ca²⁺-activated Cl⁻ channels (ANO1/TMEM16A) on the plasma membrane
Explanation
ICC pacemaker activity is driven by oscillating IP3-mediated Ca²⁺ release from the ER (through IP3 receptors and ryanodine receptors in a 'Ca²⁺ clock' mechanism). This local Ca²⁺ release activates Ca²⁺-sensitive chloride channels (ANO1, also called TMEM16A) on the plasma membrane. ANO1 conducts outward Cl⁻ (inward current), depolarizing the cell toward threshold. Once threshold is reached, L-type Ca²⁺ channels fire to generate the plateau; then repolarization occurs through K⁺ channels. ANO1 knockout mice lack GI pacemaker activity, confirming this mechanism.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.