% coupled signaling/EC for adult rat ventricular myocytes % % FIGURE REPRODUCTION MODE % Run this script and follow prompts regarding which figure in the primary paper to reproduce. % Reference: % Jeffrey J. Saucerman, Laurence L. Brunton, Anushka p. Michailova, and Andrew D. McCulloch % "Modeling beta-adrenergic Control of cardiac myocyte contractility in silico", J. Biol. Chem., Vol 278: 47977-48003 % % Copyright (2004) The Regents of the University of California % All Rights Reserved % % Last modified: 3 September 2021 % Implemented by: Shelley Fong % clear; close all; tic % ----------------------------------- % checkFigure 2a 2b 2c 2d 2e 2f 2gh 3a 3b 4a 4b 5 6a 6b checkFigure = input('Enter figure number in format ia: ', 's'); % ----------------------------------- if strcmp(checkFigure ,'2g') || strcmp(checkFigure ,'2h') checkFigure = '2gh'; end fprintf('Fig %s\n',checkFigure) saucerman_jbc2003(checkFigure); toc function saucerman_jbc2003(checkFigure) extracted_figure_path = 'figures/paperExtractedCSV/'; isoproterenol = 0.01; protocol = 0; cAMP_holding = repmat([0],50,1); PKI = repmat([0],50,1); expr_mult = repmat([0],50,1); CTX = repmat([0],50,1); vPLBKO = repmat([0],50,1); IBMX = repmat([0],50,1); data_fracPLBp = []; data_fig4 = []; data_cAMP_normal = []; data_cAMP_ACmult = []; data_cAMP_B1ARmult = []; data_cAMP_KGsadiv = []; data_cAMP_Control = []; data_cAMP_PKA_KO = []; data_cAMP_PKI_KO = []; data_CaTransient = []; data_CaTransient_PLBKO = []; % --------------- EXPERIMENTAL PROTOCOLS --------------- N = 1e3; switch checkFigure case '2a' tspan = [0,18*60]; numloops0 = 1; numloops = numloops0; isoproterenol = 0.01; case '2b' tspan = linspace(0,5*60,N); numloops0 = 8; % different isoproterenol. *2 for IBMX. numloops = numloops0*2; isoproterenol = logspace(-3,0.45,numloops0); % solution diverges at isoproterenol > 10^0.1 uM data_cAMP_ss_IBMX0 = zeros(numloops0,1); data_cAMP_ss_IBMX1 = zeros(numloops0,1); IBMX0 = [0, 100]; % uM % 270 % repeat loops to run with IBMX IBMX = [IBMX0(1)*ones(numloops0,1); IBMX0(2)*ones(numloops0,1)]; isoproterenol = [isoproterenol, isoproterenol]; case {'2c','2d'} tspan = linspace(0,60,N); numloops0 = 6; % num trials with different [cAMP] *2 for PKI. isoproterenol = ones(numloops0*2,1)*isoproterenol; cAMP_holding = logspace(-1.9, 2, numloops0); PKI0 = [0e-15, 0.052]; PKI = [PKI0(1)*ones(numloops0,1); PKI0(2)*ones(numloops0,1)]; lenPKI = length(PKI0); numloops = numloops0*lenPKI; cAMP_holding = [cAMP_holding, cAMP_holding]; data_cAMP_ss0 = zeros(numloops0*2,2); % [] data_PKA0 = zeros(numloops0*2,1); % [] data_cAMP_ss1 = zeros(numloops0*2,2); % [] data_PKA1 = zeros(numloops0*2,1); % [] case '2e' tspan = linspace(0, 60*30,N); % 30 minutes numloops0 = 20; isoproterenol = logspace(-6,0,numloops0); numloops = numloops0; case '2f' tspan = [0:0.001:60]; numloops0 = 2; % without/with isoproterenol numloops = numloops0; isoproterenol = [0, 1]; protocol = 2; case '2gh' tspan = [0:0.001:60]; numloops0 = 2; % without/with isoproterenol numloops = numloops0; isoproterenol = [0, 1]; protocol = 1; case {'3a', '3b'} numloops0 = 8; % vary isoproterenol conc if strcmp(checkFigure, '3a') tspan = linspace(0,7*60,N); isoproterenol = logspace(-3,0,numloops0); expr_mult0 = [1,3.0, 3.0, 3.0]; % [Control, ACmult, B1ARmult, cAMP_mult/K_Gsa] [1,3,3,3] IBMX0 = 1e2; else tspan = linspace(0,6*60,N); isoproterenol = logspace(-4,-0.5,numloops0); expr_mult0 = [1,1.5, 1.8, 1.9]; % [Control, ACmult, B1ARmult, cAMP_mult/K_Gsa] IBMX0 = 0; end IBMX = repmat(IBMX0,numloops0*4,1); lenx = length(expr_mult0); numloops = lenx*numloops0; expr_mult = [expr_mult0(1)*ones(numloops0,1); expr_mult0(2)*ones(numloops0,1); expr_mult0(3)*ones(numloops0,1); expr_mult0(4)*ones(numloops0,1)]; isoproterenol = repmat(isoproterenol, 1, lenx); case '4a' tspan = linspace(0, 3*60); numloops0 = 3; numloops = numloops0; isoproterenol = [1,0,1]; IBMX0 = 2.5e2; IBMX = repmat(IBMX0,numloops0,1); CTX = [0,1,1]; case '4b' tspan = linspace(0, 3*60); numloops0 = 2; isoproterenol = [1e-4, 1]; CTX = [0,0,1,1]; IBMX0 = 2.5e2; numloops = numloops0*2; isoproterenol = repmat(isoproterenol,1,2); IBMX = repmat(IBMX0,numloops,1); data_Gsa_gtp_AC = zeros(numloops,1); case '5' tspan = linspace(0, 20*60,N); % 20*60 numtrials = 3; numloops0 = 8; % different isoproterenol isoproterenol = logspace(-4,0,numloops0); isoproterenol = repmat(isoproterenol, 1, numtrials); % Control PKA_KO PKI_KO numloops = numloops0*numtrials; case '6a' tspan = [0:0.001:60]; numloops0 = 3; % normal, LCCphos only, PLB phos only. protocol = 1; numloops = numloops0; isoproterenol = ones(numloops, 1); case '6b' tspan = [0:0.001:60]; numloops0 = 4; % normal, Iso, PLBKO, Iso+PLBKO protocol = 1; assert(numloops0 == 4, 'numloops must be 4') numloops = numloops0; isoproterenol = [0,1,0,1]; vPLBKO = [0,0,1,1]; otherwise error('no figure specified'); end if false && (~strcmp(checkFigure,'2f')&&(~strcmp(checkFigure,'2gh') && (~strcmp(checkFigure,'6a') && ~strcmp(checkFigure,'6b')))) for it = 1:length(tspan) tspan(it) = tspan(it)*0.001; end end Cm = 324e-6; % uF: 207 or 324 pF % ----- Signaling model parameters ------- % b-AR/Gs module p_orig(1) = 0; %isoproterenol(n); % Ltotmax [uM] p_orig(2) = 0.0132; % sumb1AR [uM] p_orig(3) = 3.83; % Gstot [uM] p_orig(4) = 0.285; % Kl [uM] p_orig(5) = 0.062; % Kr [uM] p_orig(6) = 33.0; % Kc [uM] p_orig(7) = 1.1e-3; % k_barkp [1/sec] p_orig(8) = 2.2e-3; % k_barkm [1/sec] p_orig(9) = 3.6e-3; % k_pkap [1/sec/uM] p_orig(10) = 2.2e-3; % k_pkam [1/sec] p_orig(11) = 16.0; % k_gact [1/sec] p_orig(12) = 0.8; % k_hyd [1/sec] p_orig(13) = 1.21e3; % k_reassoc [1/sec/uM] % cAMP module p_orig(14) = 49.7e-3;% AC_tot [uM] p_orig(15) = 5.0e3; % ATP [uM] p_orig(16) = 38.9e-3;% PDEtot [uM] p_orig(17) = 0.0; % IBMXtot [uM] p_orig(18) = 0.0; % Fsktot [uM] (10 uM when used) p_orig(19) = 0.2; % k_ac_basal[1/sec] p_orig(20) = 8.5; % k_ac_gsa [1/sec] p_orig(21) = 7.3; % k_ac_fsk [1/sec] p_orig(22) = 5.0; % k_pde [1/sec] p_orig(23) = 1.03e3; % Km_basal [uM] p_orig(24) = 315.0; % Km_gsa [uM] p_orig(25) = 860.0; % Km_fsk [uM] p_orig(26) = 1.3; % Km_pde [uM] p_orig(27) = 0.4; % Kgsa [uM] p_orig(28) = 44.0; % Kfsk [uM] p_orig(29) = 30.0; % Ki_ibmx [uM] % PKA module p_orig(30) = 0.59; % PKAItot [uM] p_orig(31) = 0.025; % PKAIItot [uM] p_orig(32) = 0.18; % PKItot [uM] 0.18 p_orig(33) = 9.14; % Ka [uM] p_orig(34) = 1.64; % Kb [uM] p_orig(35) = 4.375; % Kd [uM] p_orig(36) = 0.2e-3; % Ki_pki [uM] % PLB module p_orig(37) = 10; % epsilon [none] p_orig(38) = 106; % PLBtot [uM] p_orig(39) = 0.89; % PP1tot [uM] p_orig(40) = 0.3; % Inhib1tot [uM] p_orig(41) = 54; % k_pka_plb [1/sec] p_orig(42) = 21; % Km_pka_plb [uM] p_orig(43) = 8.5; % k_pp1_plb [1/sec] p_orig(44) = 7.0; % Km_pp1_plb [uM] p_orig(45) = 60; % k_pka_i1 [1/sec] p_orig(46) = 1.0; % Km_pka_i1 [uM] p_orig(47) = 14.0; % Vmax_pp2a_i1 [uM/sec] p_orig(48) = 1.0; % Km_pp2a_i1 [uM] p_orig(49) = 1.0e-3; % Ki_inhib1 [uM] % LCC module p_orig(50) = 25e-3; % LCCtot [uM] p_orig(51) = 25e-3; % PP1lcctot [uM] p_orig(52) = 25e-3; % PP2Alcctot [uM] p_orig(53) = 54; % k_pka_lcc [1/sec] p_orig(54) = 21; % Km_pka_lcc [uM] p_orig(55) = 8.52; % k_pp1_lcc [1/sec] p_orig(56) = 3; % Km_pp1_lcc [uM] p_orig(57) = 10.1; % k_pp2a_lcc [1/sec] p_orig(58) = 3; % Km_pp2a_lcc [uM] % ---- EC Coupling model parameters ------ % universal parameters p_orig(59) = 20.8e-6; % Vmyo [uL] p_orig(60) = 9.88e-7; % Vnsr [uL] p_orig(61) = 9.3e-8; % Vjsr [uL] p_orig(62) = 1.534e-4; % ACap [cm^2] with C = 1 uF/cm^2 p_orig(63) = 310; % Temp [K] % extracellular concentrations p_orig(64) = 140; % Extracellular Na [mM] p_orig(65) = 5.4; % Extracellular K [mM] p_orig(66) = 1.8; % Extracellular Ca [mM] % current conductances p_orig(67) = 8.0; % G_Na [mS/uF] p_orig(68) = 0.35; % G_to [mS/uF] p_orig(69) = 0.07; % G_ss [mS/uF] p_orig(70) = 0.24; % G_kibar [mS/uF] p_orig(71) = 0.008; % G_kp [mS/uF] % I_Ca parameters p_orig(72) = 300; % f [1/sec] p_orig(73) = 2e3; % g [1/sec] p_orig(74) = 5187.5; % gammao [1/sec/mM] p_orig(75) = 10; % omega [1/sec] p_orig(76) = 5.823e-9*3.0; % pCa [cm/sec] p_orig(77) = 1.078e-11*3.0; % pK [cm/sec] p_orig(78) = 3e5; % Nlcc [#/cell] p_orig(79) = -0.458; % I_Ca05 [uA/uF] % pumps and background currents p_orig(80) = 1483; % k_NaCa [uA/uF] p_orig(81) = 87.5; % Km_Na [mM] p_orig(82) = 1.38; % Km_Ca [mM] p_orig(83) = 0.1; % k_sat [none] p_orig(84) = 0.35; % eta [none] p_orig(85) = 1.1; % ibarnak [uA/uF] p_orig(86) = 10; % Km_Nai [mM] p_orig(87) = 1.5; % Km_Ko [mM] p_orig(88) = 1.15; % ibarpca [uA/uF] p_orig(89) = 0.5e-3; % Km_pca [mM] p_orig(90) = 2.8e-3; % G_Cab [uA/uF] p_orig(91) = 1.18e-3; % G_Nab [uA/uF] p_orig(92) = 0; % Pns p_orig(93) = 1.2e-3; % Km_ns [mM] % Calcium handling parameters p_orig(94) = 4.7; % I_upbar [mM/sec] p_orig(95) = 3e-4; % Km_up [mM] p_orig(96) = 15; % nsrbar [mM] p_orig(97) = 2e-3; % tauon [sec] p_orig(98) = 2e-3; % tauoff [sec] p_orig(99) = 60e3; % gmaxrel [mM/sec] p_orig(100) = 0.18e-3;% dcaith [mM] p_orig(101) = 0.8e-3; % Km_rel [mM] p_orig(102) = 8.75; % CSQNth [mM] p_orig(103) = 15; % CSQNbar [mM] p_orig(104) = 0.8; % Km_csqn [mM] p_orig(105) = 5.7e-4; % tau_tr [sec] p_orig(106) = 0.07; % TRPNbar [mM] p_orig(107) = 0.05; % CMDNbar [mM] p_orig(108) = 0.07; % INDObar [mM] p_orig(109) = 0.5128e-3; % Km_trpn [mM] p_orig(110) = 2.38e-3; % Km_cmdn [mM] p_orig(111) = 8.44e-4; % Km_indo [mM] % Initial conditions and mass matrix % b-AR/Gsa module % 1 2 3 4 5 6 7 8 9 % L R Gs b1ARtot b1ARd b1ARp Gsagtptot Gsagdp Gsbg y10=[0.010; 0.01079;3.829; 0.01205;0.0; 1.154e-3;0.02505; 6.446e-4;0.02569]; m1 =[0, 0, 0, 1, 1, 1, 1, 1, 1]; % cAMP module and PKA module % 10 11 12 13 14 15 % Gsa_gtp Fsk AC PDE IBMX cAMPtot y20=[0.02241;0; 0.04706;0.0389; 0; 0.8453]; m2 =[0, 0, 0, 0, 0, 1]; % PKA module % 16 17 18 % cAMP PKACI PKACII y30=[0.2268;0.05868;8.278e-3]; m3 =[0, 0, 0]; % PLB % 19 20 21 22 % PLBp Inhib1ptot Inhib1p PP1 y40=[4.105; 0.0526; 6.3e-5; 0.838]; m4 =[1, 1, 0, 0]; % LCC module % 23 24 % LCCap LCCbp y50=[5.103e-3; 5.841e-3]; m5 =[1, 1]; % Gating variables % 25 26 27 28 29 30 31 32 33 % m h j v w x y z rto sto ssto rss sss y60=[1.4e-3;0.99; 0.99; 0.0; 0.0; 0.13; 0.96; 0.92; 1.4e-3; 1.0; 0.613; 198e-3; 0.43]; m6 =[1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1]; % Intracellular concentrations/ Membrane voltage % 38 39 40 41 42 43 44 % Ca_nsr Ca_jsr Nai Ki Cai Vm trel y70=[1.92; 1.92; 16; 145; 1.58e-4;-85.66; 0.9]; m7 =[1, 1, 1, 1, 1, 1, 1]; % Put everything together y0_orig = [y10;y20;y30;y40;y50;y60;y70]; M = diag([m1,m2,m3,m4,m5,m6,m7]); % folder for timecourse plots temp_path = 'figures/temp/'; if ~exist(temp_path,'dir') mkdir(temp_path) else % clear folder dinfo = dir(temp_path); dinfo([dinfo.isdir]) = []; filenames = fullfile(temp_path, {dinfo.name}); if length(filenames) delete( filenames{:} ) end end % convert cAMP concentration (uM) to pmol/mg % volume of one myocyte = 36.8 pL (Bers) Vmyo = 36.8e-12; fudgeFactor = 6.4; %6*15/14; % to fit with data cellsPermg = 25635.76702; %Mendez and Keys 1961 (from myocyte density) cAMP_mult = Vmyo*cellsPermg*1e6*fudgeFactor; % fprintf('fudge factor = %d for [cAMPtot]\n',fudgeFactor); % disp(numloops) parfor (n=1:numloops) % for n=1:numloops p = p_orig; y0 = y0_orig; fprintf('Loop %d/%d \n', n,numloops); CTXn = 0; plot_cAMP = false; fig6p = ''; fracPLBo = 0.9613; PLBKO = 0; switch checkFigure case {'2a', '2b', '2e'} p(1) = isoproterenol(n); if strcmp(checkFigure, '2b') p(17) = IBMX(n); plot_cAMP = true; end case {'2c','2d'} y0(16) = cAMP_holding(n); %cAMP y0(15) = cAMP_holding(n)*4; p(32) = PKI(n); case {'2f', '2gh'} p(1) = isoproterenol(n); case {'3a', '3b'} plot_cAMP = true; p(17) = IBMX(n); p(1) = isoproterenol(n); if n > numloops0 && n <= numloops0*2 p(14) = p_orig(14)*expr_mult(n); % AC_tot elseif n > numloops0*2 && n <= numloops0*3 y0(4) = y0_orig(4)*expr_mult(n); % b1AR_tot elseif n > numloops0*3 && n <= numloops0*4 p(27) = p_orig(27)/expr_mult(n); % Kgsa end case {'4a','4b'} plot_cAMP = true; p(1) = isoproterenol(n); p(17) = IBMX(n); p(12) = p_orig(12)*(0.05*CTX(n) + ~CTX(n)); % p_12 = k_hyd case '5' plot_cAMP = true; p(1) = isoproterenol(n); if n > numloops0 && n <= numloops0*2 p(30) = p_orig(30)*0.05; % PKAItot elseif n > 2*numloops0 && n <= numloops0*3 p(32) = p_orig(32)*0.05; % PKItot end case '6a' plot_cAMP = true; p(1) = isoproterenol(n); if n == 2 fig6p = 'LCC'; y0(19) = 0; elseif n == 3 fig6p = 'PLB'; y0(23) = 0; y0(24) = 0; end case '6b' p(1) = isoproterenol(n); PLBKO = vPLBKO(n); if vPLBKO(n) && false p(38) = p_orig(38)*0.00001; % PLBtot y0(19) = y0_orig(19)*0.00001; % PLBp end end options = odeset('Mass',M,'RelTol',1e-6,'MaxStep',5e-3,'Stats','off'); % -------------------- Run simulation -------------------- stp = struct(); stp.protocol = protocol; stp.p = p; stp.fig6 = fig6p; stp.PLBKO = PLBKO; stp.fracPLBo = fracPLBo; stp.checkFigure = checkFigure; [t_temp,y] = ode15s(@f,tspan,y0,options,stp); [~,datOut] = f(t_temp, y, stp); of_2fgh(n) = false; if strcmp(checkFigure, '2f') || strcmp(checkFigure, '2gh') of_2fgh(n) = true; end if (n == 1 && of_2fgh(n)) || ~of_2fgh(n) data_t1(n,:) = t_temp; data_y1(n,:,:) = y; data_I1(n,:,:) = [datOut.I_Ca, datOut.I_app]; end switch checkFigure case {'2f', '2gh'} if n == 2 data_t2(n,:) = t_temp; data_y2(n,:,:) = y; data_I2(n,:,:) = [datOut.I_Ca, datOut.I_app]; end case {'2c','2d'} if n <= numloops0 data_cAMP_ss0(n,:) = [y(end,15), y(end,16)]; data_PKA0(n,:) = y(end,17); else data_cAMP_ss1(n,:) = [y(end,15), y(end,16)]; data_PKA1(n,:) = y(end,17); end case '2e' data_fracPLBp = [data_fracPLBp, datOut.fracPLBp(end)]; case '2b' if n <= numloops0 data_cAMP_ss_IBMX0(n) = y(end,15); %[1:int:end] else data_cAMP_ss_IBMX1(n) = y(end,15); end case {'3a', '3b'} if n <= numloops0 data_cAMP_normal = [data_cAMP_normal, y(end,15)]; elseif n <= 2*numloops0 && n > numloops0 data_cAMP_ACmult = [data_cAMP_ACmult, y(end,15)]; elseif n <= 3*numloops0 && n > 2*numloops0 data_cAMP_B1ARmult = [data_cAMP_B1ARmult, y(end,15)]; else data_cAMP_KGsadiv = [data_cAMP_KGsadiv, y(end,15)]; end case {'4a','4b'} data_fig4 = [data_fig4, y(end,15)]; % cAMP_tot data_Gsa_gtp_AC(n) = datOut.Gsa_gtp_AC(end); case '5' if n <= numloops0 data_cAMP_Control = [data_cAMP_Control, y(end,15)]; elseif n <= 2*numloops0 && n > numloops0 data_cAMP_PKA_KO = [data_cAMP_PKA_KO, y(end,15)]; elseif n <= 3*numloops0 && n > 2*numloops0 data_cAMP_PKI_KO = [data_cAMP_PKI_KO, y(end,15)]; end case '6a' data_CaTransient = [data_CaTransient; y(:,42)']; case '6b' iSS = find(t_temp>tspan(end)-1,1); data_CaTransient_PLBKO = [data_CaTransient_PLBKO, max(y(iSS:end,42))]; end % plot cAMP timecourse in TEMP folder if true loop_plot = false; ip = zeros(numloops,1); legnames = cell(numloops,1); pm = cAMP_mult; ycaption = 'conc [pmol/mg]'; if plot_cAMP ip(n) = 15; legnames{n} = 'cAMP_tot'; loop_plot = true; elseif (strcmp(checkFigure, '2c') || strcmp(checkFigure, '2d')) ip(n,1) = 15; legnames{n} = 'cAMP_tot'; loop_plot = true; elseif strcmp(checkFigure, '2e') ip(n,1) = 19; legnames{n} = {'PLBp'}; pm = 1/p_orig(38); ycaption = 'conc uM'; loop_plot = true; elseif strcmp(checkFigure, '6b') ip(n,1) = 42; legnames{n} = {'calcium_i mM'}; ycaption = 'conc uM'; pm = 1; loop_plot = true; end if loop_plot figure, for j=1:length(ip(n)) plot(t_temp, y(:,ip(n,j))*pm); hold on; end hold off; legend(legnames{n}); xlabel('time') ylabel(ycaption) title(sprintf('loop %d',n)); saveas(gcf,[temp_path num2str(n) '.jpg']); end end end I_Ca1 = data_I1(1,:,1); I_app1 = data_I1(1,:,2); Cai1 = data_y1(1,:,42); Vm1 = data_y1(1,:,43); if of_2fgh I_Ca2 = data_I2(2,:,1); I_app2 = data_I2(2,:,2); Cai2 = data_y2(2,:,42); Vm2 = data_y2(2,:,43); end if exist('data_t1','var') % translate time for experiments under protocol 1 or 2 data_t1 = data_t1 - 59; end if exist('data_t2','var') % translate time for experiments under protocol 1 or 2 data_t2 = data_t2 - 59; end co = [0 0 1 1 0 0 0 1 0]; set(groot,'defaultAxesColorOrder',co, 'DefaultLineLineWidth', 4, 'DefaultLineMarkerSize',12) figure('DefaultAxesFontSize',18) switch checkFigure case '2a' dat = csvread([extracted_figure_path checkFigure '.csv'],1,0); % skip header plot(dat(:,1),dat(:,2),'bx'); hold on; plot(data_t1/60, data_y1(1,:,15)*cAMP_mult,'b'); xlabel ('Time (min)') ylabel('cAMP_{tot} (pmol/mg)'); % legend('primary data','reproduction'); case '2b' datwithIBMX = csvread([extracted_figure_path '2b_withIBMX.csv'],1,0); % skip header datwithoutIBMX = csvread([extracted_figure_path '2b_withoutIBMX.csv'],1,0); % skip header semilogx(isoproterenol(1:numloops0), data_cAMP_ss_IBMX0(1:numloops0)*cAMP_mult, 'b-'); hold on; semilogx(isoproterenol(numloops0+1:end), data_cAMP_ss_IBMX1(numloops0+1:end)*cAMP_mult, 'r-') semilogx(datwithoutIBMX(:,1),datwithoutIBMX(:,2),'bx'); hold on; semilogx(datwithIBMX(:,1),datwithIBMX(:,2),'rx'); hold on; legend('no IBMX','with IBMX','Location','east'); xlim([10e-3 10e1]); xlabel('Isoproterenol (\muM)') ylabel('cAMP_{tot} (pmol/mg)') case {'2c','2d'} denom = 2*p_orig(30); % PKAI_tot F1 = data_PKA0(1:numloops0)/denom; F2 = data_PKA1(numloops0+1:end)/denom; datSolid = csvread([extracted_figure_path checkFigure '_solid.csv'],1,0); % skip header datDashed = csvread([extracted_figure_path checkFigure '_dashed.csv'],1,0); if strcmp(checkFigure,'2c') semilogx(data_cAMP_ss0(1:numloops0,1),F1,'b'); hold on; semilogx(data_cAMP_ss1(numloops0+1:end,1),F2,'r'); semilogx(datSolid(:,1),datSolid(:,2),'bx'); hold on; semilogx(datDashed(:,1),datDashed(:,2),'rx'); hold on; hold off; legend('PKACI', 'PKACI+PKI','Location','northwest'); xlabel('cAMP_{tot} (\muM)') ylabel('PKA activation') else semilogx(data_cAMP_ss0(1:numloops0,1),log10(F1./(1-F1)),'b'); hold on; semilogx(data_cAMP_ss1(numloops0+1:end,1),log10(F2./(1-F2)),'r'); hold on; semilogx(datSolid(:,1),datSolid(:,2),'bx'); hold on; semilogx(datDashed(:,1),datDashed(:,2),'rx'); hold on; hold off; legend('PKACI', 'PKACI+PKI','Location','northwest'); xlabel('cAMP_{tot} (\muM)') ylabel('log(F/(1-F))') xlim([0.01 1]); end case '2e' dat = csvread([extracted_figure_path checkFigure '.csv'],1,0); % skip header semilogx(dat(:,1),dat(:,2),'bx'); hold on; semilogx(isoproterenol, data_fracPLBp,'b'); %hold on; xlabel('Isoproterenol (\muM)'); ylabel('frac PLBp'); % legend('primary data','reproduction','Location','east'); case '2f' datSolid = csvread([extracted_figure_path checkFigure '_solid.csv'],1,0); % skip header datDotted = csvread([extracted_figure_path checkFigure '_dotted.csv'],1,0); % skip header queryTime = tspan(end)-1; iSS = [find(tspan == queryTime), find(tspan == queryTime+0.3), length(tspan)]; plot(data_t1(1,iSS(1):iSS(2)),I_Ca1(iSS(1):iSS(2))*Cm*1e3,'b'); hold on; plot(data_t2(2,iSS(1):iSS(2)),I_Ca2(iSS(1):iSS(2))*Cm*1e3,'r'); plot(datSolid(:,1),datSolid(:,2),'bx'); hold on; plot(datDotted(:,1),datDotted(:,2),'rx'); hold on; legend('no Iso','1 \muM Iso', 'Location','southeast') ylabel('I_{Ca} (nA)') xlabel('Time (s)') case '2gh' % query Figs 2g-h datSolid = csvread([extracted_figure_path '2g_solid.csv'],1,0); % skip header datDashed = csvread([extracted_figure_path '2g_dashed.csv'],1,0); queryTime = tspan(end)-1; iSS = [find(tspan == queryTime), find(tspan == queryTime+0.3), length(tspan)]; plot(data_t1(1,iSS(1):iSS(3)),Cai1(iSS(1):iSS(3))*1e3,'b'); hold on; plot(data_t2(2,iSS(1):iSS(3)),Cai2(iSS(1):iSS(3))*1e3,'r'); hold on; plot(datSolid(:,1),datSolid(:,2),'bx'); hold on; plot(datDashed(:,1),datDashed(:,2),'rx'); hold on; ylabel('[Ca_i] (\muM)') xlabel('Time (s)') legend('no Iso', '1 \muM Iso','Location','northeast'); title('2g') saveas(gcf,'figures/F2g.jpg'); % subplot(1,2,2) set(groot,'defaultAxesColorOrder',co, 'DefaultLineLineWidth', 4, 'DefaultLineMarkerSize',12) figure('DefaultAxesFontSize',18) datSolid = csvread([extracted_figure_path '2h_solid.csv'],1,0); % skip header datDashed = csvread([extracted_figure_path '2h_dashed.csv'],1,0); plot(data_t1(iSS(1):iSS(2)), Vm1(iSS(1):iSS(2)),'b'); hold on; plot(data_t2(2,iSS(1):iSS(2)), Vm2(iSS(1):iSS(2)),'r'); hold on; plot(datSolid(:,1),datSolid(:,2),'bx'); hold on; plot(datDashed(:,1),datDashed(:,2),'rx'); hold on; legend('no Iso', '1 \muM Iso','Location','northeast'); xlabel('Time (s)') ylabel('Membrane Voltage (mV)') ylim([-100 20]) title('2h') saveas(gcf,'figures/F2h.jpg'); case {'3a', '3b'} datSolid = csvread([extracted_figure_path checkFigure '_solid.csv'],1,0); % skip header datDashed = csvread([extracted_figure_path checkFigure '_dashed.csv'],1,0); % skip header if strcmp(checkFigure, '3a') datmidDashed = csvread([extracted_figure_path checkFigure '_midDashed.csv'],1,0); % skip header datDotted = csvread([extracted_figure_path checkFigure '_dotted.csv'],1,0); % skip header end semilogx(isoproterenol(1:numloops0), data_cAMP_normal*cAMP_mult, 'b-'); hold on; semilogx(isoproterenol(numloops0+1:numloops0*2), data_cAMP_ACmult*cAMP_mult, 'r-'); hold on; semilogx(isoproterenol(numloops0*2+1:numloops0*3), data_cAMP_B1ARmult*cAMP_mult, 'g-'); hold on; semilogx(isoproterenol(numloops0*3+1:end), data_cAMP_KGsadiv*cAMP_mult, 'm-'); hold on; semilogx(datSolid(:,1),datSolid(:,2),'bx'); hold on; semilogx(datDashed(:,1),datDashed(:,2),'rx'); hold on; if strcmp(checkFigure, '3a') semilogx(datDotted(:,1),datDotted(:,2),'gx'); hold on; end if strcmp(checkFigure, '3a') semilogx(datmidDashed(:,1),datmidDashed(:,2),'mx'); hold on; end if strcmp(checkFigure, '3a') xlim([10e-4,1]); ylim([0 650]); legend(... {'Control', ... sprintf('[AC_{tot}] * %g', expr_mult0(2)), ... sprintf('[\\beta1AR_{tot}] * %g', expr_mult0(3)), ... sprintf('K_{Gs\\alpha} / %g', expr_mult0(4)),... },... 'Location','northwest','FontSize',14); else legend(... {'Control', ... sprintf('[AC_{tot}] * %g', expr_mult0(2)), ... sprintf('[\\beta1AR_{tot}] * %g', expr_mult0(3)), ... sprintf('KGsa / %g', expr_mult0(4))},... 'Location','northwest','FontSize',14); end xlabel('Isoproterenol (\muM)') ylabel('cAMP_{tot} (pmol/mg)') case '4a' dat = csvread([extracted_figure_path checkFigure '.csv'],1,0); % skip header denom = data_fig4(1); %normalise by data at Iso=1uM, CTX=0 data_fig4 = data_fig4/denom; bar([dat';data_fig4]',1) ylabel('AC activity') % cAMP_{tot} (\muM) set(gca, 'XTickLabel',{'Iso','CTX','Iso+CTX'}); legend('primary data','reproduction','Location','northwest'); case '4b' datSolid = csvread([extracted_figure_path checkFigure '_solid.csv'],1,0); % skip header datDotted = csvread([extracted_figure_path checkFigure '_dotted.csv'],1,0); % skip header denom = data_fig4(end); % normalise by data at 10uM ISO+CTX y = data_fig4/denom; x = data_Gsa_gtp_AC/p_orig(14); % p not available after for loop plot(x(1:2),y(1:2),'b-'); hold on; plot(x(3:4),y(3:4),'r-'); plot(datSolid(:,1),datSolid(:,2),'bx'); hold on; plot(datDotted(:,1),datDotted(:,2),'rx'); hold on; legend('Control','CTX','Location','northwest'); xlabel('Fractional AC activation'); % GsaGTP_{AC}/AC_{tot} ylabel('f_{cAMP}') % cAMP_{tot}/cAMP_{tot,max} for j=1:numloops protostr = sprintf('%g \\muM', isoproterenol(j)); text(x(j)+0.01,y(j)-0.03,protostr,'fontsize',16) end case '5' dat = csvread([extracted_figure_path checkFigure '_Control.csv'],1,0); % skip header datPKI = csvread([extracted_figure_path checkFigure '_PKI.csv'],1,0); datPKA = csvread([extracted_figure_path checkFigure '_PKA.csv'],1,0); semilogx(isoproterenol(1:numloops0), data_cAMP_Control*cAMP_mult, 'b-'); hold on; semilogx(isoproterenol(1:numloops0), data_cAMP_PKA_KO*cAMP_mult, 'r-'); hold on; semilogx(isoproterenol(1:numloops0), data_cAMP_PKI_KO*cAMP_mult, 'g-'); semilogx(dat(:,1),dat(:,2),'bx'); hold on; semilogx(datPKA(:,1),datPKA(:,2),'rx'); hold on; semilogx(datPKI(:,1),datPKI(:,2),'gx'); hold on; legend('Control',... 'PKA-KO', ... 'PKI-KO', 'Location','east'); xlabel('Isoproterenol (\muM)') ylabel('cAMP_{tot} (pmol/mg)') case '6a' dat = csvread([extracted_figure_path checkFigure '_both.csv'],1,0); % skip header datLCC = csvread([extracted_figure_path checkFigure '_LCC.csv'],1,0); datPLB = csvread([extracted_figure_path checkFigure '_PLB.csv'],1,0); queryTime = tspan(end)-1; iSS = [find(tspan == queryTime), length(tspan)]; plot(data_t1(1,iSS(1):iSS(2)), data_CaTransient(1,(iSS(1):iSS(2)))*1e3,'b-'); hold on; % convert mM to uM plot(data_t1(1,iSS(1):iSS(2)), data_CaTransient(2,(iSS(1):iSS(2)))*1e3,'r-'); hold on; plot(data_t1(1,iSS(1):iSS(2)), data_CaTransient(3,(iSS(1):iSS(2)))*1e3,'g-'); hold on; plot(dat(:,1),dat(:,2),'bx'); hold on; plot(datLCC(:,1),datLCC(:,2),'rx'); hold on; plot(datPLB(:,1),datPLB(:,2),'gx'); hold on; legend('PLB + LCC', 'LCC','PLB','Location','northeast'); xlabel('Time (s)') ylabel('Calcium (\muM)'); hold off; case '6b' dat = csvread([extracted_figure_path checkFigure '.csv'],1,0); % skip header d = [data_CaTransient_PLBKO*1e3]; bar([dat';d]', 1) ylabel('Calcium (\muM)'); set(gca, 'XTickLabel',{'None','Iso','PLB KO','Iso+PLB KO'}); legend('primary data','reproduction','Location','northwest'); otherwise disp('figure not specified properly'); end if ~strcmp(checkFigure, '2gh') title(checkFigure); saveas(gcf,['figures/F' checkFigure '.jpg']); end end