Fig. 6. A model of excitation—thermogenic coupling in heater cells. Thermogenesis in heater cells is proposed to occur via depolarization-induced Ca²⁺ release pathways. Nervous stimulation mediated by acetylcholine receptors (AchR) results in heater cell depolarization and DHPR—RyR1-mediated Ca²⁺ release. Increased cytoplasmic Ca²⁺ stimulates Ca²⁺ transport and ATP turnover by SERCA 1B and mitochondrial influx and efflux pathways. The physiological properties of the RyR1-slow isoform expressed in heater cells may facilitate prolonged channel openings under these conditions (high Ca²⁺ and the presence of adenine nucleotides) and promote further release of Ca²⁺ in a `futile' cycle that results in thermogenesis. Abbreviations: T-tubule, transverse-tubule; SR, sarcoplasmic reticulum; SERCA, sarco/endoplasmic reticulum Ca²⁺-ATPase; RyR, ryanodine receptor; DHPR, dihydropyridine receptor.