;;
;; _ Whole Cell Stochastic Model Reproduces the Irregularities Found
;; in the Membrane Potential of Bursting Neurons_
;;
;; Pedro V. Carelli, Marcelo B. Reyes, Jose C. Sartorelli, and Reynaldo D. Pinto
;;
;; J Neurophysiol 94: 1169 1179, 2005.
;;

(nemo-model Carelli05

  ((input v  (ica from ion-currents))

   (const Vrest   = -68)

	
   (component (type membrane-capacitance)
	      (const C_m = 1) ;; Specific membrane capacitance, 1 uF/cm^2
	      (output C_m))
		    
   (component (type decaying-pool) (name ca)

	      ;; Ca2+ concentration, uM
	      (const Ca0    = 0.5)
	      (const f      = 14.96) ;; uM/nA
	      (const tau_Ca = 200) ;; ms

	      ;; Calcium buffer
	      (d (Ca) = ((neg (1 / tau_Ca)) * ((f * ica) + Ca + (neg (Ca0))))
		 (initial 370))

	      ;; Assuming external Ca2+ concentration of 3000 uM
	      (E_Ca = (12.5 * (ln (3000 / Ca))))
	      
	      (output Ca)

	      )

   ;; Ionic conductances, mS/cm^2 
   
   (component (type ion-channel) (name Na)
	      
	      (component (type gate)

			 (hh-ionic-gate 
			  (Na  ;; ion name: exported variables will be of the form {ion}_{id}
			   (initial-m (1 / (1 + (exp ((Vrest + 25.5) / -5.29)))))
			   (initial-h (1 / (1 + (exp ((Vrest + 48.9) / 5.18)))))
			   (m-power   3)
			   (h-power   1)
			   (m-inf     (1 / (1 + (exp ((v + 25.5) / -5.29)))))
			   (m-tau     (2.64 - (2.52 / (1 + (exp ((v + 120) / -25))))))
			   (h-inf     (1 / (1 + (exp ((v + 48.9) / 5.18)))))
			   (h-tau     ((1.34 / (1 + (exp ((v + 62.9) / -10)))) *
					 (1.5 + (1 / (1 + (exp ((v + 34.9) / 3.6)))))))))
			 )
	      
	      (component (type pore)
			 (const  gbar_Na  = 200)
			 (output gbar_Na ))
	      
	      (component (type permeating-substance) (name na)
			 (const e_Na = 50)
			 (output e_Na ))
	      
	      ) ;; end Na current


   (component (type ion-channel) (name CaT)
	      
	      (component (type gate)

			 (hh-ionic-gate 
			  (CaT
			   (m-power 3) 
			   (h-power 1)
			   (initial-m (1 / (1 + (exp ((Vrest + 27.1) / -7.2)))))
			   (initial-h (1 / (1 + (exp ((Vrest + 32.1) / 5.5)))))
			   (m-inf  (1 / (1 + (exp ((v + 27.1) / -7.2)))))
			   (h-inf  (1 / (1 + (exp ((v + 32.1) / 5.5)))))
			   (m-tau  (43.4 - (42.6 / (1 + (exp ((v + 68.1) / -20.5))))))
			   (h-tau  (210 -  (179.6 / (1 + (exp ((v + 55) / -16.9))))))))
			 )

	      (component (type pore)
			 (const  gbar_CaT  = 2.5)
			 (output gbar_CaT ))
	      
	      (component (type permeating-substance) (name ca)
			 (e_CaT = E_Ca)
			 (output e_CaT ))

	      ) ;; end CaT current
   
		    
   (component (type ion-channel) (name CaS)
	      
	      (component (type gate)

			 (hh-ionic-gate 
			  (CaS
			   (m-power 3) 
			   (h-power 1)
			   (initial-m (1 / (1 + (exp ((Vrest + 33) / -8.1)))))
			   (initial-h (1 / (1 + (exp ((Vrest + 60) / 6.2)))))
			   (m-inf  (1 / (1 + (exp ((v + 33) / -8.1)))))
			   (h-inf  (1 / (1 + (exp ((v + 60) / 6.2)))))
			   (m-tau  (2.8 +  (14  / ((exp ((v + 27) / 10)) + (exp ((v + 70) / -13))))))
			   (h-tau  (120 +  (300 / ((exp ((v + 55) / 9)) + (exp ((v + 65) / -16))))))))
			 )
			   
	      (component (type pore)
			 (const  gbar_CaS  = 4)
			 (output gbar_CaS ))

	      (component (type permeating-substance) (name ca)
			 (e_CaS = E_Ca)
			 (output e_CaS ))
	      )
		    

   (component (type ion-channel) (name KCa)

	      (component (type gate)

			 (hh-ionic-gate 
			  (KCa
			   (m-power 4) 
			   (h-power 0)
			   (initial-m  ((Ca / (3 + Ca)) * (1 / (1 + (exp ((Vrest + 28.3) / -12.6))))))
			   (m-inf      ((Ca / (3 + Ca)) * (1 / (1 + (exp ((v + 28.3) / -12.6))))))
			   (m-tau      (180.6 - (150.2 / (1 + (exp ((v + 46) / -22.7))))))))
			 )
     
	      (component (type pore)
			 (const  gbar_KCa  = 5)
			 (output gbar_KCa ))

	      (component (type permeating-substance) (name k)
			 (const e_KCa = -80)
			 (output e_KCa ))
	      )

	      
   (component (type ion-channel) (name Kd)
		       
	      (component (type gate)

			 (hh-ionic-gate 
			  (Kd
			   (m-power 4) 
			   (h-power 0)
			   (initial-m (1 / (1 + (exp ((Vrest + 12.3) / -11.8)))))
			   (m-inf  (1 / (1 + (exp ((v + 12.3) / -11.8)))))
			   (m-tau  (14.4 - (12.8 / (exp ((v + 28.3) / -19.2)))))))
			 )

	      (component (type pore)
			 (const  gbar_Kd  = 100)
			 (output gbar_Kd ))

	      (component (type permeating-substance) (name k)
			 (const e_Kd = -80)
			 (output e_Kd ))
	      )

				  
   (component (type ion-channel) (name A)
		       
	      (component (type gate)

			 (hh-ionic-gate 
			  (A
			   (gbar 50)
			   (m-power 3) 
			   (h-power 1)
			   (initial-m (1 / (1 + (exp ((Vrest + 27.2) / -8.7)))))
			   (initial-h (1 / (1 + (exp ((Vrest + 56.9) / 4.9)))))
			   (m-inf  (1 / (1 + (exp ((v + 27.2) / -8.7)))))
			   (h-inf  (1 / (1 + (exp ((v + 56.9) / 4.9)))))
			   (m-tau  (23.2 - (20.8 / (1 + (exp ((v + 32.9) / -15.2))))))
			   (h-tau  (77.2 - (58.4 / (1 + (exp ((v + 38.9) / -26.5))))))))
			 )

	      (component (type pore)
			 (const  gbar_A  = 50)
			 (output gbar_A ))

	      (component (type permeating-substance) (name non-specific)
			 (const e_A = -80)
			 (output e_A ))
	      )

   (component (type ion-channel) (name H)

	      (component (type gate)

			 (hh-ionic-gate 
			  (H
			   (m-power 1) 
			   (h-power 0)
			   (initial-m (1 / (1 + (exp ((Vrest + 75) / 5.5)))))
			   (m-inf  (1 / (1 + (exp ((v + 75) / 5.5)))))
			   (m-tau  (2.2 / ((exp ((v + 169.7) / -11.6)) + (exp ((v - 26.7) / 14.3)))))))
			 )

	      (component (type pore)
			 (const  gbar_H  = 0.1)
			 (output gbar_H ))

	      (component (type permeating-substance) (name non-specific)
			 (const e_H = -20)
			 (output e_H ))
	      )

   
   (component (type ion-channel) (name Leak)
	      
	      (component (type pore)
			 (const  gbar_Leak  = 0.1)
			 (output gbar_Leak ))
	      
	      (component (type permeating-substance) (name non-specific)
			 (const e_Leak = -50)
			 (output e_Leak ))
	      
	      ) ;; end leak current

   ))