Fig 1.
The ions flow generated in Piezo2 channels under different indentation depths. triangle line: experimental results from [36], solid line: simulation results(d0 = 5.8μm, d0 = 6.7μm, d0 = 7.0μm, d0 = 7.3μm, d0 = 7.6μm, d0 = 7.9μm).
Table 1.
Parameters of Piezo2 channels.
Table 2.
Parameters of internal Ca2+ channels.
Fig 2.
The membrane potential dynamics of one Merkel cell under the rectangular current pulses.
(A) Negetive current pulses step in 8.14pA (experimental current step in 10pA). (B) Membrane potentials change under negative current pulses. The solid lines are simulation results, and the triangles are experimental results from [21]. (C) Positive current pulses step in 8.14pA, Green line: 9 × 8.14pA, blue line: 14 × 8.14pA. (D) Membrane potentials change under positive current pulses. The solid lines are the simulation results, and the triangles are experimental results from [21]. The parameters of ion channels are seen in Table 3.
Table 3.
Fig 3.
The membrane potential dynamics of one Merkel cell with different properties under the rectangular current pulses.
(A) The changes of membrane potential of experimental results from [24]. (B) Membrane potentials change under current pulses in simulation, (C) The changes of membrane potential under the condition of reduced Ca2+ concentration in external solutions from [24]. (D) Membrane potentials change under current pulses in simulation at CCa,out = 5uM. blue line: 27.14pA, red line: 54.28pA, yellow line: 67.85pA. The parameters of ion channels are seen in Table 3.
Fig 4.
The Ca2+ transients in Merkel cells under high K+ stimulation.
(A) The fluorescence intensity change of Ca2+ under high K+ solution [23]. (B) The cytoplasm concentration of Ca2+ change under high K+ solution: cK,out increases by 130nM and cNa,out reduces by 130nM in simulation. (C) The fluorescence intensity change of Ca2+ under high K+ solution by adding thapsigargin (TG), which is a specific blocker of Ca2+ pumps on ER, to deplete intracellular Ca2+ stores [23]. (D) The cytoplasm concentration of Ca2+ change under high K+ solution in simulation by setting PRYR = 0, Pleak = 0, , and Ppump,ER = 0. The parameters of ion channels are seen in Table A in S1 Appendix.
Fig 5.
The Ca2+ transients in Merkel cells under hypotonic shock.
(A) The fluorescence intensity change of Ca2+ under hypotonic shock by removing 30mM mannitol in external solution [22]. (B) The cytoplasm concentration of Ca2+ changes under hypotonic shock by removing 30mM mannitol in external solution in simulation. The parameters of ion channels are seen in Table A in S1 Appendix.
Fig 6.
The roles of Cav1.2, Cav2.1 channels, and Ca2+ pumps in membrane potential regulation under the rectangular current pulse(114.1pA,200ms).
(A) The changes of membrane potential with different , yellow line:
, purple line:
, green line:
, blue line:
. (B) The changes of membrane potential with different
, yellow line:
, purple line:
, green line:
, blue line:
. (C) The changes of membrane potential with different PCapump. yellow line: PCapump = 3 × 10−16, purple line: PCapump = 3 × 10−15, green line: PCapump = 6 × 10−15, blue line: PCapump = 3 × 10−14(mol/(cm2 ⋅ ms)).
Fig 7.
The roles of Kv1.4, Kv4.2, BKCa, and KDR channels in membrane potential regulation under the rectangular current pulse(114.1pA,200ms).
(A) The changes of membrane potential with different . yellow line:
, purple line:
, green line:
, blue line:
. (B) The changes of membrane potential with different
. yellow line:
, purple line:
, green line:
, blue line:
. (C) The changes of membrane potential with different gBKCa. yellow line: gBKCa = 0, purple line: gBKCa = 0.18, green line: gBKCa = 1.8, blue line: gBKCa = 18(mS/cm2). (D) The changes of membrane potential with different gKDR. yellow line: gKDR = 0, purple line: gKDR = 0.01, green line: gKDR = 0.1, blue line: gKDR = 1(mS/cm2).
Fig 8.
The roles of Ryanodine receptors, IP3 receptors, ER Ca2+ pumps and MCU pumps in membrane potential regulation under the rectangular current pulse(114.1pA,200ms).
(A) The changes of membrane potential with different PRYR. yellow line: PRYR = 0, purple line: PRYR = 0.08, green line: PRYR = 0.8, blue line: PRYR = 8(cm/ms). (B) The changes of membrane potential with different . yellow line:
, purple line:
, green line:
, blue line:
(cm/ms). (C) The changes of membrane potential with different PCapump,ER. yellow line: PCapump,ER = 0, purple line: PCapump,ER = 0.7 × 10−18, green line: PCapump,ER = 0.7 × 10−17, blue line: PCapump,ER = 0.7 × 10−16(mol/(cm2⋅ms)). (D) The changes of membrane potential with different PMCU(PMCU/PMNCX = 5). yellow line: PMCU = 0, purple line: PMCU = 0.5 × 10−15, green line: PMCU = 0.5 × 10−14, blue line: PMCU = 0.5 × 10−13(mol/(cm2 ⋅ ms)).
Fig 9.
The roles of Cav1.2, Cav2.1 channels, and Ca2+ pumps in Ca2+ transients under the rectangular current pulse(114.1pA,60s).
(A) The changes of Ca2+ concentration in the cell with different , yellow line:
, purple line:
, green line:
, blue line:
. (B) The changes of Ca2+ concentration in the cell with different
, yellow line:
, purple line:
, green line:
, blue line:
. (C) The changes of Ca2+ concentration in the cell with different PCapump. yellow line: PCapump = 0, purple line: PCapump = 0.3 × 10−15, green line: PCapump = 0.3 × 10−14, blue line: PCapump = 0.3 × 10−13(mol/(cm2 ⋅ ms)).
Fig 10.
The roles of Kv1.4, Kv4.2, BKCa and KDR channels in Ca2+ transients under the rectangular current pulse(114.1pA,60s).
(A) The changes of Ca2+ concentration in the cell with different . yellow line:
, purple line:
, green line:
, blue line:
. (B) The changes of Ca2+ concentration in the cell with different
. yellow line:
, purple line:
, green line:
, blue line:
. (C) The changes of Ca2+ concentration in the cell with different gBKCa. yellow line: gBKCa = 0, purple line: gBKCa = 0.18, green line: gBKCa = 1.8, blue line: gBKCa = 18(mS/cm2). (D) The changes of Ca2+ concentration in the cell with different gKDR. yellow line: gKDR = 0, purple line: gKDR = 0.01, green line: gKDR = 0.1, blue line: gKDR = 1(mS/cm2).
Fig 11.
The roles of Ryanodine receptors, IP3 receptors, ER Ca2+ pumps and MCU pumps in Ca2+ transients under the rectangular current pulse(114.1pA,200ms).
(A) The changes of Ca2+ concentration in the cell with different PRYR. yellow line: PRYR = 0, purple line: PRYR = 0.08, green line: PRYR = 0.8, blue line: PRYR = 8(cm/ms). (B) The changes of membrane potential with different . yellow line:
, purple line:
, green line:
, blue line:
(cm/ms). (C) The changes of Ca2+ concentration in the cell with different PCapump,ER. yellow line: PCapump,ER = 0, purple line: PCapump,ER = 0.7 × 10−18, green line: PCapump,ER = 0.7 × 10−17, blue line: PCapump,ER = 0.7 × 10−16(mol/(cm2 ⋅ ms)). (D) The changes of Ca2+ concentration in the cell with different PMCU(PMCU/PMNCX = 5). yellow line: PMCU = 0, purple line: PMCU = 0.5 × 10−15, green line: PMCU = 0.5 × 10−14, blue line: PMCU = 0.5 × 10−13(mol/(cm2 ⋅ ms)).
Table 4.
Parameters of endocytosis and exocytosis.
Fig 12.
Responses of Merkel cells under compression in 100ms.
(A) The Merkel cell was compressed at a depth d0 with a speed of 1um/ms. The dynamic change of (B) cortex stress, (C) currents generated in the Piezo2 channels, (D) membrane potential, (E) currents generated in Cav2.1 channels, (F) currents generated in Cav1.2 channels, (G) cytoplasmic concentration of Ca2+, (H) exocytosis rate, (I) number of cytoplasmic vesicles, and (J) Endoplasmic reticulum concentration of Ca2+(blue:d0 = 3μm, red:d0 = 4μm, yellow:d0 = 5μm, cyan:d0 = 6μm, green:d0 = 7μm).
Fig 13.
Responses of Merkel cells under compression in 20s.
(A) The Merkel cell was compressed at a depth d0 with a speed of 1um/ms. The dynamic change of (B) cortex stress, (C) currents generated in the Piezo2 channels, (D) membrane potential, (E) cytoplasmic concentration of Ca2+, (F) number of cytoplasmic vesicles, (G) exocytosis rate, and (H) Endoplasmic reticulum concentration of Ca2+(blue:d0 = 3μm, red:d0 = 4μm, yellow:d0 = 5μm, cyan:d0 = 6μm, green:d0 = 7μm).