Figure 4. Effect of PA SMC K_V current density and the interplay with K_IR current on V_m dynamics at rest and during potassium challenge.

(A) Combined contribution of K_IR and K_v currents in healthy and diseased models during rest and [K⁺]_o stimulus. Activation of K_IR current by [K⁺]_o and hyperpolarization is accounted: $I_{\mathit{\text{Kir}}}=\frac{G_{\mathit{\text{Kir}},\mathit{\text{max}}}(V_m-E_K)}{1+\text{exp}(\frac{(V_m-V_{K_{\mathit{\text{IR}}},0.5})}{k_{\mathit{\text{Kir}}}})};G_{\mathit{\text{Kir}},\mathit{\text{max}}}=G_{\mathit{\text{Kir}}}{[K^{+}]}_o^{0.5}$ where G_kir,max is the maximal K_IR conductance. Solid lines show the sum of the two currents at rest, and dashed lines are during elevation of [K⁺]_o from 3 to 8 mM. The shaded regions show the range of voltages within which K_IR current increases more than K_V current decreases during the K⁺ stimulus, i.e. the resting V_m window where the K⁺ challenge will result in hyperpolarization. As K_V current density increases (from SAH, red lines; to CTL black lines; to CADASIL, blue lines) the window shrinks in size and shifts to more hyperpolarized potentials. (B) Representative simulation using the model of PA SMCs from Figure 3. SMCs from CTL (black line), CADASIL (blue line) and SAH (red line) conditions hyperpolarize following an increase in extracellular K⁺, [K⁺]_o, from 3 mM to 8 mM. The change in membrane potential is less for CADASIL as a result of the more hyperpolarized resting V_m prior to the K⁺ challenge. G_KIR = 0.76 [nS/(mM)^0.5]; k_KIR = 7 [mV]; V_KIR,0.5= E_K+12 [mV].