Figure 3. Relationship between myogenic tone and membrane potential.

(A) Values of membrane potential and myogenic tone at different intravascular pressure (mm Hg) from CADASIL (TgNotch3^R169C, blue triangles) and SAH (red circles) animals are consistent with the linear regression obtained from CTL animals (black triangles represent CTL mice from (17) and black circles represent CTL rats from (6)) showing a similar relationship between tone and membrane potential. (B) A detailed model of SMC membrane potential and Ca²⁺ dynamics was adapted from (102) and modified by incorporating the K_V1 current of PA SMCs from CTL animals (Figure 2), while adjusting other transmembrane currents (K_IR, NSC, VDCC, NaK, PMCA) to produce resting V_m and Ca²⁺ concentration in agreement with experimental data (17,103). The effect of altered K_V1 channel density in CADASIL (blue triangles) and SAH (red triangles) was examined assuming all other model parameters remain the same as in CTL (black circles). (C) The effect of increasing pressure was simulated by depolarizing SMC membrane through increasing Na⁺ permeability (P_Na). Model simulations, in agreement with the corresponding experiments in (A), show differences between CADASIL and SAH animals in V_m (bottom) and Ca²⁺ (top) as pressure increases and highlight the inhibitory role of K_V channels and the effect K_V channel density on myogenic tone. Parameters as in reference (102) except: P_VDCC=6.3×10⁻⁵ cm/s; P_NaNSC=1.23×10⁻⁶ cm/s; I_PMCA=8.58 pA; I_NaK=7.76 pA/pF; G_KIR = 0.5 nS/(mM)^0.5; G_Na,leak=0.12 nS; C_m = 12.8 pF.